Expression of a high level of myeloperoxidase (MPO) as a sole myeloid marker in acute leukemias that express typical lymphoblastic markers is unusual. Herein we report 5 cases of MPO+, otherwise typical acute lymphoblastic leukemia (ALL) without the expression of other myeloid markers. In most cases, MPO positivity was detected in more than 20% of blasts by immunologic (flow cytometric) and enzymatic testing. The striking feature of most of these cases is a morphologic picture reminiscent of that seen in Burkitt-like B-cell ALL with basophilic cytoplasm and vacuoles but no expression of surface immunoglobulin. All cases responded to ALL therapy and should be distinguished from myeloid leukemia and from Burkitt leukemia/lymphoma.