It is commonly believed that the insulin receptor mainly mediates the metabolic effects of insulin, whereas the closely related IGF-I receptor is considered a major factor for the regulation of cell proliferation. Experimental and epidemiological evidence indicates, however, that insulin and insulin receptors may play an important role in breast cancer. This article reviews evidence indicating that (a) insulin receptors are overexpressed in human breast cancer, (b) insulin stimulates growth in breast cancer cells, (c) cells transfected with human insulin receptor may acquire a ligand-dependent transformed phenotype, and (d) breast cancer is associated with insulin resistance and hyperinsulinemia. These findings may open new possibilities in breast cancer prevention, prognosis assessment, and therapy. (Trends Endocrinol Metab 1997; 8:306-312). (c) 1997, Elsevier Science Inc.