The French-American-British (FAB) classification of acute leukemias is based on the light microscopic detection of myeloperoxidase (MPO) activity in blast cells. Cells with MPO activity in > 3% of cells are classified as acute myeloid leukemia (AML) and usually express myeloid cell surface antigens. We describe a case of acute leukemia in which the blast cells have lymphoid morphology, ultrastructure, immunophenotype, and molecular rearrangements, but express significant amounts of MPO. We discuss the incidence, features, and outcome of MPO-positive acute lymphoblastic leukemia (ALL).