BACKGROUND Malignant fibrous histiocytoma of bone, a relatively rare primary malignant neoplasm occurring in bone, is a distinct clinicopathologic entity formerly included in the category of osteosarcoma or fibrosarcoma. A series of patients treated at the Mayo Clinic for malignant fibrous histiocytoma of bone was studied to determine whether the prognosis for this disease is different from that of osteosarcoma and whether treatment should be different. METHODS The bone tumor files of the Mayo Clinic were reviewed for examples of malignant fibrous histiocytoma of bone. Clinical records and histologic slides were reviewed for 81 patients. Roentgenograms of 13 patients were available for review. RESULTS Patients with malignant fibrous histiocytoma of bone ranged in age from 6 to 81 years. The region most commonly affected was the knee. Seventy-eight percent of the lesions arose de novo and 22% in preexisting conditions. Histologically, most of the tumors were classified as the storiform pleomorphic type, although other histologic subtypes were identified. The prognosis depended on the types of surgical margins involved. Patients with wide or radical margins had a better prognosis than patients in whom the margins were contaminated. Some patients who received radiation therapy alone became long term survivors. CONCLUSIONS The overall prognosis for patients with malignant fibrous histiocytoma was not found to be significantly different from that described for patients with osteosarcoma in recent series. However, at least in this small series, some patients with malignant fibrous histiocytoma had a good response to radiation therapy. Osteosarcoma is generally considered radioresistant.