Serial cryostat sections of 160 human breast lesions and of 9 lymph-node metastases were studied by indirect immunofluores-cence. We used monoclonal antibodies (MAbs) to lining-epithelium-specific keratin 8 and to myoepithelium-specific keratin 17 in combination with polyclonal and monoclonal antibodies to major basement membrane components, laminin, collagen type IV, entactinhidogen, and large heparan sulfate proteoglycan (perlecan) core protein. Continuous basement membranes adjacent to a basal layer of keratin-17-positive myoepithelial cells were typical for normal, benign and in situ carcinomatous structures. In invasive and metastatic structures, always formed by keratin-8-positive tumor cells, basement membranes were found only rarely and with conspicuous fragmentations. This lack of basement membranes correlated with loss of myoepithelium identified by staining for keratin 17. In comedo structures of invasive ductal carcinomas and in papillary carcinomas, fibrovascular complexes with numerous blood vessels and deposition of basement membrane material were often seen in the stroma. lmmunomorphological analysis of 41 cases of doubtful diagnosis at intra-operative biopsy was also performed. A combination of MAbs to keratins 8 and 17, and to basement membrane components, made it possible to distinguish between morphologically similar benign and malig-nant proliferations and to detect single-cell invasion of the stroma. This combination of antibodies may be recommended as an auxiliary immunomorphological tool for differential diagno-sis of intra-operative breast biopsies in dubious cases.