Epithelial cells can be distinguished from various non-epithelial cells by the presence of keratin-type intermediate-sized filaments, which can be detected by immunofluorescence microscopy, using antibodies to alpha-keratin. In the present study, two types of antibodies were obtained. One of them was specific for alpha-keratin (mol. wt. 49,000 to 69,000 daltons) in whole epidermis, and the other for alpha-keratin (mol. wt. 62,000 and 69,000 daltons) in prickle and granular cells but not in basal cells. Four cases of so-called mixed tumour of the skin were studied by immunofluorescence microscopy using these antibodies. Tumour cells nests of cuboidal and polygonal cells, tubular structures and keratinous cysts reacted with these antibodies, as did individually-dispersed tumour cells within the myxoid and chondroid matrix. These results indicate that all the tumour cells of the so-called mixed tumour of the skin are of epithelial origin. Differences in staining intensity between these tumor cells and their specificity for these two antibodies are discussed with reference to keratin differentiation in tumour cells.