Can Identical Twins Be Male and Female?

Identical twins nearly always share the same biological sex, but in extraordinarily rare circumstances they can develop as one male and one female. These cases arise from genetic accidents that happen after the fertilizing event that created the shared embryo, or from an unusual form of twinning that blurs the line between identical and fraternal. Each pathway is different, and understanding them sheds light on how sex determination works in the first place.

Why Identical Twins Are Usually the Same Sex

Monozygotic twins form when a single fertilized egg splits into two embryos during the first couple of weeks after conception. Because both embryos descend from the same original cell, they carry the same set of chromosomes, including the same pair of sex chromosomes. If the zygote is XY, both twins are genetically male; if it is XX, both are genetically female. The timing of the split affects whether the twins share a placenta or an amniotic sac, but it does not normally change their chromosomes.¹ This is why opposite-sex twins are almost always fraternal, meaning they developed from two separately fertilized eggs. When a doctor sees one boy and one girl in a twin pair, the default assumption is dizygotic twinning. But “almost always” is not “always.”

Losing a Y Chromosome After Fertilization

The best-documented route to opposite-sex identical twins involves an error in cell division that happens very early in embryonic development, before or around the time the embryo splits into two. If the original zygote is 46,XY and one cell loses its Y chromosome during mitosis, the embryo becomes a mosaic: some cells carry the normal 46,XY set, while others carry only 45,X. When the embryo then divides into twins, the two resulting embryos can end up with very different proportions of each cell line. One twin may inherit mostly 46,XY cells and develop as a typical male, while the other inherits mostly 45,X cells and develops as female, often with features of Turner syndrome.

A report on two such twin pairs found exactly this pattern. In both cases, the female twin was identified at birth because of signs of Turner syndrome, and cytogenetic testing revealed 45,X/46,XY mosaicism. In the first pair, the female twin’s skin and gonadal tissue showed only 45,X cells, while her blood cells were a mix of 45,X and 46,XY. The researchers concluded that a mitotic error leading to Y chromosome loss before, during, or after the twinning event accounted for the discordant karyotypes.²

A related mechanism starts not with a normal XY zygote but with an abnormal one. If the original fertilized egg is 47,XXY, a post-zygotic loss of the Y chromosome can produce an embryo with both 46,XX and 47,XXY cell lines. If that embryo then splits into twins, the distribution of the two cell lines between them can be lopsided enough to yield one twin who develops as female and another who develops as male with Klinefelter-type features.³ In both scenarios, the twins trace back to the same fertilization event, which is the defining criterion for monozygotic twinning. Yet one ends up chromosomally and anatomically male and the other female.

Sesquizygotic Twins and the Space Between Identical and Fraternal

There is a second, even rarer route that challenges the neat categories of identical versus fraternal. In 2019, researchers described a pregnancy that produced one male and one female twin sharing a single placenta, a feature strongly associated with identical twinning. Genetic testing revealed something unexpected: the twins were maternally identical (they shared 100 percent of their mother’s DNA) but shared only about 78 percent of their father’s genome. The explanation was that a single egg had been fertilized by two different sperm simultaneously, producing a cell mass with three sets of chromosomes that then divided into two embryos. The researchers called these twins “sesquizygotic,” meaning they fell genetically between monozygotic and dizygotic.⁴

Because two sperm were involved, one could carry an X chromosome and the other a Y, which is how the twins ended up as different sexes despite sharing a placenta and all of their maternal DNA. This is not the same thing as traditional identical twinning, but it is not straightforward fraternal twinning either. Sesquizygotic twins are a genuinely intermediate category that had only been hypothesized before this case was confirmed with modern genomic tools. Whether additional sesquizygotic pairs exist undetected in the population remains an open question; the only reason this pair was identified was the unusual combination of a shared placenta with opposite sexes, which prompted deeper genetic analysis.

Same Chromosomes, Different Anatomy

Perhaps the most striking cases involve twins who are chromosomally identical, both carrying a 46,XY karyotype, yet one develops a male body and the other a female body. This happens when a condition affecting how the body responds to sex hormones strikes one twin but not the other.

Complete androgen insensitivity syndrome (CAIS) is one such condition. A person with CAIS has XY chromosomes and testes that produce testosterone, but their cells cannot respond to androgens. The result is a body that develops along female lines externally: breasts develop at puberty, a vagina is present, but there is no uterus or ovaries. A case report described 46,XY twins where one was a typical male with normal male development and the other was an 18-year-old presenting as female with breasts and a vagina but no uterus. Chromosomal analysis confirmed both were 46,XY, and the female twin was diagnosed with CAIS.⁵

In another reported case, monozygotic 46,XY twins were discordant for sex phenotype, and the SRY gene (the primary switch for male development on the Y chromosome) was present and unmutated in both. The researchers confirmed monozygosity through DNA analysis at multiple genetic markers. Their conclusion was that the female twin’s condition could be explained by a mutation in a different gene involved in the sex-determination cascade, or by hidden mosaicism involving 45,X cell lines present in the gonads but not detected in blood.⁶ These cases drive home an important point: chromosomes set the stage, but many downstream genes and hormonal signals are needed to complete sexual development. A glitch in any of them can redirect the outcome, even when the starting chromosomes are identical.

Chimerism and Why Appearances Can Deceive

Chimerism adds yet another layer of complexity. A chimera is a person whose body contains cells from two genetically distinct sources. This can happen naturally when fraternal twin embryos exchange cells through shared blood vessel connections in the placenta, or when two early embryos fuse into one. If the original embryos were one XX and one XY, the resulting person can carry both XX and XY cell lines, which may lead to ambiguous or discordant sex development.

Twin chimerism through shared placental blood supply is not as unusual as it sounds. One large study found that about 8 percent of twins and 21 percent of triplets had blood-group chimerism, meaning they carried blood cells from their co-twin.⁷ Most of the time this chimerism is limited to blood cells and has no visible effect. But in rare cases involving IVF, where multiple embryos are transferred, tetragametic fusion chimerism can occur: two embryos physically merge into one individual. If those embryos were different sexes, the resulting person can have XX/XY chimerism throughout their body, potentially with differences in sex development.

Chimerism matters to the question of opposite-sex “identical” twins because it can create diagnostic confusion. A pair of twins who look like one boy and one girl sharing a placenta might initially be assumed to be an extraordinary case of opposite-sex monozygotic twins. Deeper genetic testing could reveal that the twins are actually fraternal but chimeric, or that one twin is a chimera from a vanished triplet embryo. Modern genomic testing can usually sort this out, but it was much harder before such tools were available, and some older case reports in the literature may have been misclassified.

Polar Body Twinning

A less well-known theoretical pathway involves polar bodies. During egg maturation, a cell called a polar body is expelled. Normally it degenerates, but in rare instances a polar body can be fertilized by a separate sperm. If both the egg and the polar body are successfully fertilized, the result is twin embryos that share the mother’s genetic contribution (to varying degrees) but have completely different paternal contributions. Researchers confirmed a version of this in a case where a malformed twin was found to carry two maternally derived chromosome sets and both of the mother’s tissue-type markers, with evidence of fertilization by a different sperm from its normal co-twin.⁸

Because the two sperm involved in polar body twinning can carry different sex chromosomes, the resulting twins could be opposite sexes. These twins would be genetically closer than ordinary fraternal twins on the maternal side but fully different on the paternal side. Modeling has estimated that the overall genetic correlation between first-polar-body twins would be around 0.38, which is actually slightly less similar than typical fraternal twins on average, though this depends on where chromosomal crossover events occurred during the mother’s egg formation.⁹ Polar body twinning is exceedingly rare and difficult to confirm without detailed genetic analysis, so its true frequency in the population is unknown.

How Fertility Treatments Fit In

Assisted reproduction has been suspected of increasing the rate of monozygotic twinning, which could theoretically increase the chances of these rare chromosomal accidents. Procedures like IVF, ICSI, and embryo biopsy involve physical manipulation of eggs and embryos, and some researchers have speculated this handling could make embryo splitting more likely. A large 10-year retrospective study, however, found no statistically significant difference in monozygotic twinning rates among different assisted-reproduction techniques. The micromanipulation involved in ICSI, preimplantation genetic testing, and surgical sperm extraction did not raise the rate compared to standard IVF.¹⁰

That said, fertility treatments do increase the number of multiple pregnancies in general, and transferring multiple embryos creates more opportunities for chimerism. The case of XX/XY chimerism described earlier involved an IVF-conceived individual where three embryos were transferred, raising the possibility that a vanished third embryo fused with or exchanged cells with the surviving twins.⁷ So while fertility treatments may not make monozygotic splitting itself more common, the overall landscape of unusual twin and higher-order pregnancies is richer in IVF populations simply because more embryos are in play.

Telling Twins Apart in the Lab and the Courtroom

Standard DNA profiling cannot distinguish monozygotic twins from each other, which has real consequences in forensic and legal settings. If one identical twin commits a crime and leaves DNA at the scene, conventional testing will match both twins equally. Researchers have shown that ultra-deep next-generation sequencing can resolve this by identifying extremely rare somatic mutations, essentially single-letter DNA changes that arose in one twin after the embryo split. In one paternity case involving twin brothers, this approach found five such mutations present in the father and child but absent in the uncle, establishing which twin was the biological parent.¹¹

For twins discordant in sex, identification is obviously simpler in most contexts, but the underlying genetic testing still matters for medical care. Understanding whether a female-presenting twin has 45,X mosaicism versus complete androgen insensitivity versus chimerism determines her medical follow-up, hormone management, and cancer screening needs. A self-report questionnaire can reliably classify most twins as identical or fraternal, with one study confirming that questionnaire-based zygosity assignment matched DNA results for about 97 percent of twin pairs.¹² But the unusual cases discussed in this article are precisely the ones where questionnaires fail and detailed molecular testing is the only way to figure out what actually happened.

Gender Identity in Twin Research

The question of biological sex in twins is distinct from gender identity, but twin studies have contributed to our understanding of both. A register-based population study in Sweden examined gender dysphoria among twins and found that among 67 twin siblings of individuals diagnosed with gender dysphoria, all 10 who also had gender dysphoria were from opposite-sex twin pairs rather than same-sex pairs. Among same-sex co-twins, none had gender dysphoria. For comparison, only about 0.16 percent of non-twin siblings had the diagnosis.¹³

A pooled analysis of twin pairs took a broader view, finding that monozygotic twins were concordant for transgender identity at a rate of about 21 percent, compared to roughly 9 percent for dizygotic twins. The much higher concordance in identical twins suggests a substantial genetic contribution to gender diversity. Interestingly, when the researchers compared same-sex and opposite-sex dizygotic pairs, the concordance rates were similar (about 9 percent and 8 percent), which did not support the idea that prenatal sex hormone exposure from a male co-twin plays a major role.¹³ Case reports of monozygotic female twins discordant for transsexualism, where one identifies as male and the other does not, further illustrate that even genetically identical individuals sharing the same prenatal environment can diverge in gender identity.¹⁴

These findings sit alongside the chromosomal and hormonal stories discussed earlier. Identical twins can end up with different biological sex through rare genetic accidents, and they can end up with different gender identities through mechanisms that are still being worked out. Both phenomena underscore that the path from a fertilized egg to a person’s experienced sex and gender involves far more steps, and far more opportunities for variation, than most people realize.

1
PubMed. The timing of monozygotic twinning: a criticism of the common model
2
PubMed. Monozygotic twins with 45,X/46,XY mosaicism discordant for phenotypic sex
3
PubMed. Discordant sex in monozygotic XXY/XX twins: a case report
4
PubMed. Molecular Support for Heterogonesis Resulting in Sesquizygotic Twinning
5
PubMed Central. Complete androgen insensitivity syndrome in twins with discordant phenotypes: a case report and review of the literature
6
ScienceDirect. 46,XY monozygotic twins with discordant sex phenotype
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PubMed Central. Embryonic origin of XX/XY chimerism in an in vitro fertilization–conceived individual
8
PubMed. Genetic studies of an acardiac monster: evidence of polar body twinning in man
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PubMed. Genetic expectations of polar body twinning
10
PubMed Central. Pregnancy and neonatal outcomes of monozygotic twins resulting from assisted reproductive technology: a 10-year retrospective study
11
Forensic Science International: Genetics. Finding the needle in the haystack: Differentiating “identical” twins in paternity testing and forensics by ultra-deep next generation sequencing
12
PubMed Central. Verification of self-report of zygosity determined via DNA testing in a subset of the NAS-NRC twin registry 40 years later
13
PubMed Central. Gender dysphoria in twins: a register-based population study
14
Springer Link. Two monozygotic twin pairs discordant for female-to-male transsexualism