AbstractKeratin, a fibrous protein in eukaryotic epithelial cells, consists primarily of intermediate filaments, of which at least 19 immunologically distinct proteins have been characterized. The identification of keratin is essential to establishing the epithelial origin of a given cell type or its tumor derivatives. Histologic tinctorial tests for keratin have not been widely applied because of lack of specificity and sensitivity. Rhodamine B fluorescence demonstrates well differentiated keratin in many epithelial cells and tumors. Immunocytochemical staining with broad range antibodies and epithelial membrane antigen demonstrates most epithelial moieties. By electron microscopy, the identification of tight junctions, desmosomes and tonofibrils helps establish the epithelial lineage of a tumor. (The J Histotechnol14:51, 1991)