BACKGROUND: The results of clinical laboratory tests are an essential component of medical decision-making. To guide interpretation, test results are returned with reference intervals defined by the range in which the central 95% of values occur in healthy individuals. Clinical laboratories often set their own reference intervals to accommodate variation in local population and instrumentation. For some tests, reference intervals change as a function of sex, age, and self-identified race and ethnicity. METHODS: In this work, we develop a novel approach, which leverages electronic health record data, to identify healthy individuals and tests for differences in laboratory test values between populations. RESULTS: We found that the distributions of >50% of laboratory tests with currently fixed reference intervals differ among self-identified racial and ethnic groups (SIREs) in healthy individuals. CONCLUSIONS: Our results confirm the known SIRE-specific differences in creatinine and suggest that more research needs to be done to determine the clinical implications of using one-size-fits-all reference intervals for other tests with SIRE-specific distributions.