Ovarian hormones have been implicated in a number of neoplastic conditions. Chronic anovulation syndrome, a spontaneous biologic experiment of unopposed secretion of estrogen by the ovaries, was identified in a cohort of 1270 patients, and the risk of these patients having neoplasia was studied. Of the 1270 patients studied, 30 had a subsequent malignancy develop; the expected number was 29.8. When the individual types of subsequent malignancy were analyzed, the endometrium was the only site at increased risk. The relative risk of developing carcinoma of the endometrium after the diagnosis of chronic anovulation syndrome is 3.1 (95% confidence interval 1.1 to 7.3). The long-term risk of developing adenocarcinoma of the endometrium might be considered when treating patients who have this syndrome.