Cancer is often discussed in terms of common forms, such as breast, lung, and prostate malignancies. However, the vast majority of cancer types are statistically rare. Oncology recognizes hundreds of distinct disease entities that affect only a small fraction of the population annually. While individually uncommon, these diseases collectively account for a significant public health burden. Understanding their definition, specific examples, and the challenges they present is necessary for advancing cancer care.
Defining Rarity in Oncology
The classification of a cancer as “rare” is based on its incidence rate—the number of new cases diagnosed within a specific population each year. In Europe, the accepted threshold is fewer than six new diagnoses per 100,000 people annually. This definition was proposed by the Surveillance of Rare Cancers in Europe (RARECARE) project to provide a consistent basis for research and clinical management.
The National Cancer Institute (NCI) in the United States defines rare cancer as one that occurs in fewer than 15 out of every 100,000 people per year. This threshold translates to fewer than 40,000 individuals diagnosed annually in the U.S. Although the specific numbers differ, these classifications group together approximately 200 to 300 distinct disease types. Collectively, rare malignancies represent about one-quarter of all cancer diagnoses made worldwide each year.
Examples of Extremely Rare Malignancies
The rarest cancers have incidence rates far below the general definition of rarity. Adrenocortical carcinoma (ACC) is one example, arising in the outer layer of the adrenal gland, which produces hormones like cortisol. This malignancy is exceptionally uncommon, with an approximate incidence of only one case per million people in the United States annually. ACC is often associated with symptoms related to hormone overproduction, which can complicate its initial diagnosis.
Chordoma is another extremely infrequent malignancy, a slow-growing cancer that originates from remnants of the notochord, the precursor to the spine. This tumor typically occurs along the spine, most often at the base of the skull or in the lower back (sacrum). The incidence rate is estimated to be between 0.08 and 0.5 cases per 100,000 people each year, making it one of the rarest bone and soft tissue tumors.
Parathyroid carcinoma, a cancer of the small glands near the thyroid that regulate calcium levels, is among the least common endocrine malignancies. Its global incidence is reported to be as low as 3.5 to 5.7 diagnoses per 10 million people per year. This translates to an incidence below 0.1 per 100,000, placing it at the extreme end of the rarity spectrum. Symptoms are frequently related to high levels of calcium in the blood, which can mask the underlying tumor.
Even certain cancers that primarily affect children are considered statistically rare because of the low overall cancer rate in that age group. For instance, hepatoblastoma, the most common liver cancer in children, affects approximately 1.5 out of every million people each year. These examples illustrate that the rarest cancers originate in highly specific tissues or occur in very small patient populations.
Diagnostic Hurdles for Rare Cancers
The low incidence of these diseases creates significant barriers to timely and accurate diagnosis. The initial symptoms of rare cancers often mimic those of much more common, non-cancerous conditions. Clinicians in general practice may not immediately consider a rare malignancy, leading to a substantial delay between symptom onset and a correct diagnosis. This prolonged process often results in the disease being more advanced when finally identified.
A lack of familiarity among general pathologists and oncologists also contributes to misdiagnosis. Since individual specialists may encounter an extremely rare tumor only a few times in their careers, there is a risk of incorrect pathological classification. For complex cases, specialized pathology review is often necessary to confirm the diagnosis, adding time and complexity to the patient’s journey. Advanced molecular and genomic testing is increasingly relevant for guiding the diagnosis of these rare tumors.
Treatment and Research Gaps
Once a rare cancer is diagnosed, patients face challenges related to treatment availability and expertise. Unlike common cancers with well-established protocols, treatment guidelines for rare malignancies are often based on limited evidence or may not exist at all. This scarcity of data means healthcare providers have less certainty when making clinical decisions. The most effective therapies are often found at highly specialized cancer centers, requiring patients to travel significant distances for expert care.
Research into these diseases is hampered by the small patient population, which makes conducting traditional, statistically powerful clinical trials extremely difficult. Recruiting a sufficient number of participants for a single study is often logistically impractical. This challenge is compounded by the lack of commercial feasibility for pharmaceutical companies, as the limited market reduces the incentive to invest in developing new drugs. Efforts to overcome these gaps include international collaborations and the use of adaptive trial designs, which allow researchers to test multiple treatments simultaneously and learn from smaller patient cohorts.