A distinctly different entity from the now well-delineated malignant fibrous histiocytoma (MFH) of bone is the MFH histopathologic subtype of osteogenic sarcoma. Although uncommon, recently the authors have encountered six cases of this neoplasm, in each of which the soft tissue component was devoid of bone elements and was microscopically indistinguishable from MFH of bone or soft tissue. Neoplastic osteoid and woven bone were present in the osseous component of each tumor, however. Radiologically, the lesions generally were osteoblastic but focally osteolytic with features typical of osteogenic sarcoma. Pain was the most common presenting symptom. There was no age or sex predilection. Immunocytochemical staining showed strong positivity with alpha-1-antichymotrypsin within malignant bizarre giant cells and occasional neoplastic osteoblasts in five cases. The biological behavior followed a very aggressive course. Four of the six patients developed pulmonary metastases 6 to 12 months after initial surgery; one patient presented initially with pulmonary metastases. Adequate tumor sampling as well as optimal correlation with clinical and radiographic information are required to distinguish the MFH subtype of osteogenic sarcoma from MFH of bone, both being high-grade neoplasms, however.