The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a patient registry, wherein the diagnoses of multiple sclerosis (MS) are unverified. We compared self-reported diagnoses of registry participants to physician-reported diagnoses, and with diagnoses based on medical records review. Registry participants with more than one of the following: age of onset <10 or >50 years, no bladder symptoms or fatigue, or zero or more than four relapses in the last year, were considered atypical. All others were considered typical. We sent letters to participants describing the study, surveyed treating physicians regarding the participants' diagnosis, and reviewed medical records. Diagnosis was classified by the McDonald and Poser criteria. Of the 240 participants sampled, 109 were in active registry status with accurate contact information. Of these, 52 consented, 29 refused and 28 did not respond (weighted response rate 76.3+/-4.5%). Some 37 of 38 physician surveys confirmed the diagnosis of MS (98.8+/-1.2%). After reviewing 41 medical records, we classified 53.2+/-8.9% of participants as definite MS, 16.9+/-6.8% as possible MS, while the remainder had insufficient data for diagnostic confirmation. We confirmed a diagnosis of MS in 98.7+/-1.3% of participants based on records review, physician survey or telephone interview, supporting the validity of the diagnoses reported by NARCOMS participants.