The incidence of endometrial cancer has increased rapidly during recent years, paralleling the increased postmenopausal use of estrogens. The relation of endometrial cancer to disease conditions in which estrogens are elevated and three case-control epidemiologic studies suggest the likelihood of a cause-and-effect relation between estrogen use and endometrial cancer. These studies and New York State Cancer Registry data further suggest that the incidence will continue to rise in coming years. A thorough reevaluation of the medical indications for estrogen replacement therapy is urgently needed. Women with long-term exposure to estrogens should have periodic cancer screening examinations.