Endometrial carcinoma does not arise in or from demonstrably normal endo-metrium. A progression of changes, including cystic hyperplasia, adenomatous hyperplasia, anaplasia and carcinoma in situ usually precedes the development of actual carcinoma. This was observed in both retrospective and prospective studies. Similar changes may also be found in the noncancerous endometrium associated with endometrial carcinoma. Similar constitutional changes were observed in patients with endometrial carcinoma and endometrial hyperplasia and suggest probable overactivity of the anterior pituitary gland. Unopposed estrogenic stimulation appears related to the development of both endometrial hyperplasia and endometrial carcinoma, whether occurring naturally or given therapeutically. In animals both of these types of lesions were produced by estrogen administration and by application of carcinogenic substances. Although unusual, adenocarcinoma may arise from an abnormal focus in the patient still ovulating. In the presence of secretory endometrium this may present difficult diagnostic problems.