Atypical fibroxanthoma is a malignant fibrohistiocytic neoplasm that develops most commonly on sun-exposed skin of elderly individuals. A number of different variants have been described, ranging from a purely spindle cell type to a xanthomatous form. We recently observed an unusual variant of atypical fibroxanthoma in which there were numerous osteoclast-like multinucleated giant cells. Histologically, there was a diffuse spindle cell neoplasm in the dermis exhibiting fibrohistiocytic differentiation associated with inflammatory cells. The neoplastic spindle cells were markedly pleomorphic and many were in mitosis, some being tripolar and tetrapolar. In addition to these features, which are common in atypical fibroxanthoma, there were numerous multinucleated giant cells scattered throughout the lesion with features resembling normal osteoclasts. Epithelioid cells with features of histiocytes were seen in association with these cells. No osteoid was observed, however, that suggested monocyte-macrophage differentiation. The histologic appearance of this lesion was reminiscent of the giant cell variant of malignant fibrous histiocytoma, also termed malignant giant cell tumor of soft parts. Thus, osteoclast-like giant cells may be seen in atypical fibroxanthoma. These cells probably represent multinucleated histiocytes rather than true osteoclasts. It is important to recognize this variant to avoid confusion with other malignant soft tissue neoplasms.