Although associations between autoimmune disorders (AIs) and the development of myeloid neoplasms have been described, the pathologic features and natural history of these malignancies have not been well characterized. We evaluated whether patients with AIs with acute myeloid leukemia (AML) were similar in nature to patients traditionally considered to have therapy-related AML (t-AML). Twenty-three patients with AML with a documented prior AI were included in our analysis. Median age at AML diagnosis was 59 years (range 32-78 years), and four patients were men (17%). Median latency between AI diagnosis and AML was 7.0 years. Ten patients (43%) had normal cytogenetics and six patients (26%) had favorable risk disease. In patients older than 65, all four patients had a normal karyotype. Median follow-up for all patients was 19.8 months (range 1.8-100.4 months), with 12 patients alive at last follow-up and median overall survival for all patients of 68.1 months. The encouraging survival data lend support to the notion that AML in patients with AIs appears to have characteristics and outcome more analogous to de novo than t-AML.