Fourteen biopsy specimens from 10 patients with atypical fibroxanthoma were studied with the peroxidase-antiperoxidase method for binding of S-100 antibody. Six specimens from 4 patients were minimally positive. The S-100-positive cells were observed in greatest concentrations at the periphery of the lesions and were associated with perivascular inflammatory cells. By this method, there does not appear to be a Langerhans'' cell type of atypical fibroxanthoma. The S-100 antibody can help differentiate desmoplastic juvenile melanoma and malignant melanoma from atypical fibroxanthoma.