Glycodelin, a 28-kd human glycoprotein found in glandular epithelial cells of endometrium and seminal vesicle, was originally considered specific for the reproductive tract. Glycodelin has significant amino-acid sequence homology with beta-lactoglobulins from various species. We report herein the expression of glycodelin in normal and neoplastic glandular epithelia outside the reproductive tract including breast, sweat glands, parabronchial glands, hidradenoma, and pancreatic cystadenoma. The localization of glycodelin in highly differentiated acinar epithelia led us to investigate a possible role for glycodelin in epithelial organization. Transfection of glycodelin cDNA into MCF-7 breast cancer cells induced a dramatically altered growth behavior with formation of acinar configurations and an inability to grow in semisolid media because of apoptosis. The glycodelin-expressing cells also displayed strongly up-regulated expression of markers of organized epithelia, such as cytokeratins 8 and 18 as well as E-cadherin, and changes in intracellular distribution of beta-catenin. The rate of proliferation was also suppressed. These results show that, besides being a product of glandular epithelial cells, expression of glycodelin is accompanied by the acquisition of a phenotype of organized glandular epithelium.