Fourteen biopsy specimens from ten patients with atypical fibroxanthoma were studied with the peroxidase-antiperoxidase method for binding of S-100 antibody. Six specimens from four 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, it appears that there is not a Langerhans' cell type of atypical fibroxanthoma. The S-100 antibody can help differentiate desmoplastic juvenile melanoma and malignant melanoma from atypical fibroxanthoma.