Acute monocytic leukemia (M5) is a subtype of acute myeloid leukemia (AML) with two distinct morphologic subcategories, M5a and M5b. We compared the immunophenotype, cytogenetics and clinical outcome of AML M5 with non-M5 AML and also compared M5a with M5b. One hundred and twelve M5 (76 M5a, 36 M5b) and 726 non-M5 cases were identified and treated on protocols at our institution. There were no significant differences in immunophenotype between M5a and M5b. Translocation 11q23 was the sole abnormality in 18.6% of M5 and 3.2% of non-M5 (p<0.001). Trisomy 8 was also more prevalent in M5 (16.9%) than in non-M5 (8.7%; p=0.03). There was no significant difference in karyotypes between M5a and M5b. The complete remission rate was 70% for AML M5 and 57% for non-M5 AML (p=0.03). There was no significant difference in median overall survival or disease free survival for patients with M5 versus non-M5, M5a versus M5b. Our data indicate that the prognosis of AML M5 is similar to non-M5 AML and that M5a and M5b do not differ in immunophenotype, cytogenetics or clinical outcome.