The lineage assignment is a prerequisite for successful therapy of acute leukemia because the optimal therapeutic agents and schedules are quite different between acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The most reliable marker for AML has been thought to be myeloperoxidase (MPO). We describe here two patients who were initially diagnosed with ALL owing to the negative light microscopic reaction for peroxidase and the positive reaction of T-lymphoid markers. While these patients were successfully treated by ALL-directed therapy and survived in remission for more than 5 years, ultrastructural study using preserved specimens retrospectively revealed that some blasts had MPO-positive granules. We suggest that some cases of acute leukemia with MPO-positive blasts detected only by electron microscopy, especially when accompanied by T-lymphoid markers, will benefit from ALL-directed therapy.