We report a case of a large, deep-seated, diagnostically difficult angiomatoid fibrous histiocytoma. The neoplastic cells were positive for vimentin, calponin, CD99, and, focally, for desmin and contained intertwining cytoplasmic processes joined by desmosomelike junctions. Fusion of codon 175 of the gene to codon 110 of the gene was detected by reverse transcription-polymerase chain reaction. Because identical fusion of the and genes has been recently reported in another case of angiomatoid fibrous histiocytoma, fusion of these genes may be characteristic for at least a subset of these tumors.