Ninety-five patients diagnosed as having stage I endometrial carcinoma (EC) were divided into two groups, one with associated adenomatous hyperplasia (AH; group 1) and the other without (group 2). Adenomatous hyperplasia results from estrogenic stimulation of the endometrium. Therefore, patients in group 1 are considered to have an estrogen-related EC. Group 1 included 49 patients with an average age of 59; group 2 included 46 patients with an average age of 65. Review of the histologic characteristics of EC showed that group 1 tumors are better differentiated and less invasive and that their morphology is closer to the normal glandular structure of the endometrium. Group 2 tumors are less well differentiated, more often invade the myometrium, and include histologic variants such as papillary, clear cell, and anaplastic carcinoma that are dissimilar from the glandular structure of the normal endometrium. Mucinous adenocarcinomas and the presence of stromal foam cells were found to be associated with group 1 EC. Progesterone receptors (PR) were measured in a sample of 30 patients. They were present in all cases of group 1 ranging from 50 to 2,400 fmol/mg protein and absent or very low (30-190 fmol/mg protein) in group 2. All EC with stromal foam cells had high PR (380-2,400 fmol/mg protein). This study confirms that estrogen-related EC is generally a better differentiated and less aggressive tumor and suggests that there are two types of EC. The tumors not related to estrogens, which are histologically more malignant, were seen in an older age group of patients. In addition to the currently accepted methods of clinical evaluation of EC patients, defining the morphologic and biochemical characteristics of two types of EC may contribute to the management of EC, now the most prevalent cancer of the female pelvis. The patients known to be at risk for endometrial carcinoma, identifiable by abnormal hormonal manifestations (obesity, infertility, and other conditions related to hyperestrogenism) as well as those receiving exogenous estrogens are likely to develop a better differentiated and less aggressive form of neoplasia. It would be important to elaborate a system of early detection of EC in the group of elderly patients with no signs of hyperestrogenism prone to develop the less differentiated and biologically more aggressive tumors.