Summmary We have studied 12 cases of cutaneous atypical fibroxanthoma using immunohistochemistry to demonstrate lysozyme, α-1-antitrypsin, S-100-protein, receptors for peanut agglutinin, and intermediate filaments. Results were compared with immunostaining in 24 cases of other so-called fibrohistiocytic tumours. In addition 2 cases of atypical fibroxanthoma and 6 cases of fibrohistiocytic tumours were stained by monoclonal antibodies specific for the monocyte cell lineage (Ki-Ml, Ki-M2, Ki-M6, Ki-M7, Ki-M8, OKM-l and Leu-M1) and double-stained by monocyte-markers and Ki-67. The immunophenotype of atypical fibroxanthoma was rather similar to the marker profile found in malignant fibrous histiocytoma. All atypical fibroxanthomas were positive for vimentin and negative for epithelial markers. Monocyte lineage-specific determinants could be demonstrated in varying amounts in cells suggestive of being reactive. In contrast proliferating - Ki-67 positive - cells did not express monocyte/macrophage related antigens in atypical fibroxanthoma and malignant fibrous histiocytoma both. As to the histogenesis of these tumours our findings speak in favour of a derivation from primitive mesenchymal cells rather than from histiocytes.