We report the clinical and pathologic findings in one case of mast cell leukemia observed in a series of 60 patients with systemic mast cell disease. The leukemic variant of systemic mast cell disease is rapidly fatal (mean duration of survival, less than 6 months) in contrast to most nonleukemic cases, which follow an indolent clinical course. On the basis of our case and eight previously reported cases, mast cell leukemia is characterized by a substantial increase in atypical mast cells in the peripheral blood, diffuse infiltration with atypical mast cells in the bone marrow, a strong association with peptic ulcer disease, prominent constitutional symptoms, and hepatosplenomegaly. These cases should be distinguished from malignant mastocytosis without a substantial number of circulating atypical mast cells and also cases of acute nonlymphocytic leukemia that arise in the background of systemic mast cell disease.