The clinical, histologic, and immunohistochemical features of 37 cases of atypical fibroxanthoma (AFX) are presented. Patients ranged in age from 13 to 95 years (mean, 69). Thirty AFXs occurred on the head and neck, and seven lesions developed on the trunk or extremities. The morphologic spectrum varied from a predominant spindle cell pattern with focal cellular pleomorphism to numerous bizarre epithelioid cells with multinucleated giant cells. The spindle cell component in these lesions ranged from 10 to 90% of the constituent cells. Most (31 of 37) AFXs also contained pleomorphic giant cells. Small numbers of S-100-positive dendritic cells were present in 11 cases. Five cases showed variable reactivity with antifactor- XIIIa. Fifteen (41%) of the AFXs stained for muscle- specific actin or smooth muscle actin and 21 (57%) expressed CD68 (detected with monoclonal KP1), a monocyte-macrophage marker. Reactivity for these antigens was seen in all lesional cell types (spindled, epithelioid, and bizarre). Four immunologic profiles were observed: CD68 only (13 cases), actin only (7 cases), double positives (8 cases), and double negatives (9 cases). No significant differences in staining characteristics were observed in the head and neck versus the trunk and extremity lesions. These results expand the immunohistochemical spectrum of AFX, suggest the concept of heterogenous bimodal “fibrohistiocytic” and “myofibroblastic” phenotypes, and provide further evidence that an integrative, nonalgorithmic approach is necessary in the analysis of these and other spindle cell cutaneous lesions.