Systemic mastocytosis is a rare and occasionally aggressive condition that raises major diagnostic challenges. We report a case in a 72-year-old patient in whom the diagnosis of malignant mastocytosis required two bone marrow smears and three bone marrow biopsies examined using specific staining techniques. Despite interferon therapy, a mast-cell sarcoma of the sternum developed 1 year after symptom onset, followed 1 year later by acute myeloblastic leukemia, which was rapidly fatal.