Cellular interactions with the extracellular matrix are an important factor in the development and progression of many types of cancer. Dystroglycan is a cell surface receptor for several extracellular matrix proteins and plays a central role in the formation of basement membranes in tissues. Because abnormalities in the structure and function of basement membranes are hallmarks of metastatic disease, we examined the status of dystroglycan expression in prostate and breast tumors. In 15 cases of surgically resected prostate cancer, we noted reduced expression of dystroglycan as judged by intensity of immunohistochemical staining. This reduction was most pronounced in high-grade disease. We found similar results in 6 cases of mammary ductal adenocarcinoma, suggesting that reduced expression of dystroglycan may be a conserved feature of epithelial neoplasia. These data suggest that reduced expression of dystroglycan in prostate and breast cancers may lead to abnormal cell-extracellular matrix interactions and thus contribute to progression to metastatic disease.