The purpose of this study was to advance our knowledge of the histogenesis of spontaneous mammary tumours in laboratory mice. Normal mammary tissue and 19 spontaneous mammary tumours from adult female mice were examined using monoclonal and polyclonal antibodies differing in their recognition of various cytokeratin intermediate filament proteins (CKs). All neoplasms were intraductal and were invasive carcinomas with a tubular, papillary, cystic or solid growth pattern. CK8-positive reactions were detected in the normal alveolar and ductal epithelia and CK5- and CK14-positive reactions were seen in myoepithelial cells of nonlactating mammary glands. Positive staining for CK5 and CK8 was detected in all tumours and CK14 was expressed in those with a papillary pattern. Comparisons between non-lactating glands and tumours indicated that the neoplasms were well or moderately differentiated, there was no squamoid differentiation and that they arose from the alveoli and duct system, not the myoepithelial cells.