Keratins, or cytokeratins, represent a family of more than 20 different polypeptides which are important markers of epithelial cell differentiation. This review deals with the use of keratin immunohistochemistry in the study of pancreatic cell differentiation. Exocrine acinar cells and endocrine islet cells are well-differentiated cells which express the keratin combination 8 and 18, whereas the less-differentiated cells of the ductal tree are characterized by the additional expression of keratin 7, keratin 19, and, in the rat, keratin 20. Keratin expression is stable and can be used for cell identification after isolation and culture, and in clinical or experimental injury. The intercalated ductal cells and centroacinar cells are inconspicuous unless specific immunohistochemical markers, such as keratins, are used. In conditions where there is morphogenetic differentiation such as in fetal life, or where transdifferentiation is occurring, keratins have been used to trace the origin and fate of pancreatic cells.