Datasets from large health maintenance organizations (HMOs), particularly those with established cancer registries that report to the Surveillance, Epidemiology, and End Results program, are potentially excellent resources for studying melanoma epidemiology and outcomes. However, generalizability of the findings beyond HMO-based populations has not been well studied. We compared melanoma patient, tumor, and treatment characteristics at Kaiser Permanente Northern California and Henry Ford Healthcare Systems with those of corresponding regional, state, and national registry-reported melanoma databases. We identified all melanoma cases diagnosed at Kaiser Permanente Northern California (1996–2009) and Henry Ford Healthcare Systems (1996–2007) and ascertained patient (age, sex, race, and ethnicity), tumor (site, size, laterality, invasiveness, depth, ulceration, subtype, and stage), and treatment (surgery and radiation) variables from health system cancer registries. Registry data were obtained from Surveillance, Epidemiology, and End Results databases for the reporting period ending in November 2011. We found that melanoma cases arising in HMO settings generally have comparable patient, tumor, and treatment characteristics to regional, state, and national cases. An important difference included improved reporting of race information at HMO sites. Melanoma studies using data derived from select HMOs are potentially generalizable to local, state, and national populations, and may be better situated for studying racial–ethnic disparities.