The aim of the present study was to explore the origin of cloacogenic carcinoma in the anal canal by immunohistochemical methods. We compared cytokeratin polypeptide expression of a cloacogenic carcinoma to normal and epithelia, to anal squamous cell carcinoma and to basal and squamous cell carcinoma of the skin, using a battery of monoclonal anti-cytokeratin, polypeptide-specific antibodies. Our results indicate that cloacogenic carcinoma expresses cytokeratin polypeptides similar to those of the basal layer of anal squamous epithelium, of the anal transitional zone epithelium and of a layer of basal cells in the anal glands. Thus we concluded that each of the above cell types may be the cell of origin of cloacogenic carcinoma.