To characterize acute megakaryocytic leukemia (FAB M7 AML), we identified 37 patients with M7 AML treated at M.D. Anderson Cancer Center between 1987 and 2003 and compared them with 1800 patients with non-M7, non-M3 AML treated during the same period. The median age of the M7 AML group was 56 years (range, 21-78 years); 22 patients (59%) had an antecedent hematologic disorder or myelodysplastic syndrome or both, and 7 patients (19%) had previously received chemotherapy for other malignancies. Extensive bone marrow fibrosis was found in 23 patients (62%). Poor cytogenetic characteristics were observed in 49% of patients with M7 AML versus 33% of others (P < .001). Complete remission rates were 43% with M7 AML and 57% with non-M7 AML (P = .089). Median overall survival (OS) was 23 and 38 weeks, respectively (P = .006). Median disease-free survivals were 23 versus 52 weeks, respectively (P < .001). By multivariate analysis, M7 AML was an independent adverse prognostic factor for OS, independent of other factors including cytogenetic abnormalities (hazard ratio 1.51, P = .049). These results confirm the poor prognosis of M7 AML and indicate that other biologic characteristics beyond cytogenetic abnormalities likely play a role in this disease.