A 71-year-old woman with multiple myeloma was successfully managed for 8 years with melphalan (total dose 2056 mg). She developed a refractory anemia (myelodysplastic state), which terminated in acute eosinophilic leukemia. This form of acute leukemia, induced by chemotherapy, appears to be very rare. The cytogenetic changes, including 5q- and monosomy 7, were similar to those observed in other patients with acute nonlymphocytic leukemia as a secondary malignancy following treatments of other primary tumors.