We performed a multi-institutional retrospective analysis of the morphologic features, immunophenotype, cytogenetics, and BCR-ABL transcript characterization of cases of Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML). We compared these cases with cases of documented chronic myelogenous leukemia in myeloid blast crisis (CML-MBC). Patients with Ph+ AML were less likely to have splenomegaly or peripheral basophilia and had lower bone marrow cellularity and myeloid/erythroid ratios than patients with CML-MBC. Additional specific cytogenetic abnormalities that typically occur in CML-MBC were less common in Ph+ AML. Of 7 patients with Ph+ AML treated with imatinib mesylate, 6 showed at least a partial hematologic response, but the responses were of a short duration (median, 2.5 months). The median survival of patients with Ph+ AML was 9 months, similar to that of patients with CML-MBC (7 months). Ph+ AML is a rare aggressive acute leukemia with some features distinct from CML-MBC.