A study was undertaken to investigate changing trends in the microscopic patterns of endometrial carcinoma and to compare the biologic characteristics of those cases associated with and without estrogen usage. After each case was reviewed independently and in a random order by at least 2 pathologists, a diagnosis of cancer was agreed on in 274 patients who had been treated by 5 gynecologists at the Massachusetts General Hospital between 1940 and 1971. Six microscopic patterns were identified (adenocarcinoma, adenoacanthoma, atypical adenoacanthoma, adenosquamous carcinoma, clear-cell adenocarcinoma, and undifferentiated carcinoma). The frequency of each pattern relative to the other 5 changed only slightly during the 30-year interval. The tumors that developed in estrogen users were more highly differentiated than those that developed in nonusers (P< 0.005) and were found at an earlier average age (P< 0.02). That the adenoacanthoma was associated with estrogen usage more frequently (51%) than any other tumor type (P< 0.02) may reflect, in part, a similar and lower mean age of estrogen users (56 years) and patients with adenoacanthoma (55 years) compared with that of nonusers with the other forms of tumors (60–67 years). Although the overall 5− and 10-year survival rates of the estrogen users were higher than those of the nonusers, the differences between the 2 groups disappeared when the grade of the neoplasm was considered.