What If One Test Is Positive and One Is Negative?

When a person receives two diagnostic tests for the same condition, and one returns a positive result while the other is negative, the situation can be confusing. This conflicting outcome, known as diagnostic ambiguity, highlights that no medical test is perfectly accurate. Understanding the reasons for this discrepancy is the first step toward resolving the uncertainty and determining the true health status. Interpretation requires considering the underlying scientific and clinical factors that contribute to the final result.

Understanding Test Accuracy and Uncertainty

The primary reason for conflicting test results is that every diagnostic assay has limitations measured by two core statistical values: sensitivity and specificity. Sensitivity refers to a test’s ability to correctly identify true positives, minimizing the number of false negatives (missed cases). Specificity, conversely, represents a test’s ability to correctly identify true negatives, minimizing false positives (mistakenly indicating the presence of a condition). These two measures often exist in a trade-off; for example, a test designed to be extremely sensitive might sacrifice some specificity, leading to more false alarms. The inherent imperfection in balancing these factors means a definitive, 100% accurate test is rare, leaving room for contradictory outcomes.

Technical Reasons for Conflicting Results

Discrepancies often arise from differences in how the two tests function, especially when comparing a highly accurate laboratory test to a rapid point-of-care test. A clear example is the difference between a molecular test, such as a Polymerase Chain Reaction (PCR) assay, and a rapid antigen test. The PCR test is highly sensitive because it amplifies tiny amounts of genetic material, which can result in a positive finding even if the patient is no longer infectious. The rapid antigen test, which detects viral proteins, is generally less sensitive and more likely to return a false negative early in the infection cycle when the viral load is low. A scenario where the antigen test is negative but the PCR is positive often occurs late in recovery, where the PCR is detecting residual, non-infectious fragments.

Pre-Analytical Errors

Beyond the methodology, errors that occur before the sample reaches the analytical machine are a frequent source of conflicting results. These pre-analytical errors can include incorrect sample collection, such as a nasal swab that does not gather enough material, leading to a false negative result. Errors in handling and storage are also common, where a delay in transporting the sample or improper temperature control can cause the specimen to degrade, potentially leading to inaccurate results. Other technical issues include mislabeling the specimen, using an incorrect collection container, or the presence of substances in the sample that interfere with the test’s chemical reaction.

How Medical Context Influences Interpretation

When a physician is faced with conflicting results, the patient’s medical context becomes the primary tool for interpretation. This clinical context involves synthesizing the test results with the patient’s symptoms, medical history, and physical examination findings. For instance, a positive test result for a condition in a patient who has no symptoms and no known risk factors is viewed with higher suspicion for being a false positive. Physicians operate under the principle that they must treat the patient and not simply the test result, meaning a result that does not align with the person’s health status is often disregarded until confirmed.

The prevalence of the condition in the population also significantly influences which result is considered more likely to be correct. The lower the prevalence of the disease, the higher the chance that a positive result is actually a false positive, even with a highly specific test. Conversely, if a test is performed during an outbreak or on a person with a known high-risk exposure, the chance that a negative result is a false negative increases. This process of using the pre-test probability is an implicit part of clinical decision-making.

Next Steps for Resolving Diagnostic Ambiguity

The immediate action following conflicting results is to consult with the healthcare provider who ordered the tests. The physician can evaluate all the variables, including the specific test limitations and the patient’s clinical picture, to develop a plan for resolution. This plan almost always involves a third, confirmatory test, which should ideally employ a different scientific principle than the first two assays.

This confirmatory testing is a secondary verification process that often uses a gold-standard technique with higher specificity to definitively rule out a false positive. If an infection is suspected, a strategy of watchful waiting and retesting may be recommended, especially if the initial negative test was suspected to be a false negative due to testing too early. Retesting a few days later can provide clarity, as the condition may have progressed enough to be reliably detected by the original assay. The goal is to obtain a result that aligns with the overall clinical evidence to ensure an accurate diagnosis and appropriate course of action.