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Purpose: Several reports in the literature have shown that, compared with endometrioid adenocarcinoma, patients with papillary serous (PS) and clear cell (CC) histologic features do worse. However, it is unclear whether the outcome of PS/CC cancer is different from that of poorly differentiated endometrioid cancer. The purpose of this study was to compare the outcome between PS/CC and endometrioid International Federation of Gynecology and Obstetrics (FIGO) Grade 3 cancer and was limited to patients with Stage I–II uterine carcinoma.Methods and Materials: Between November 1987 and September 1999, 83 patients with Stage I endometrial cancer and Stage II occult endometrial cancer were treated with simple hysterectomy and high-dose-rate intravaginal brachytherapy. Forty-one patients (49%) had FIGO Grade 3 endometrioid tumors (Group 1) and 42 (51%) had PS/CC histologic features (Group 2). The mean age was 63 years (range 30–89). Comprehensive surgical staging was done in 23 (28%) of 83 patients. Capillary space-like invasion (CSLI) was seen in 24 (29%) of 83 patients. The median dose of intravaginal brachytherapy when used alone was 21 Gy in 3 fractions. Additional external beam radiotherapy was given to 42 (51%) of 83 patients to 45 Gy. The two groups were balanced with regard to age, race, comprehensive surgical staging, amount of myometrial involvement, CSLI, lower uterine segment involvement, cervical involvement, and use of external beam radiotherapy. The median follow-up was 46 months (range 4–147).Results: The pattern of relapse was as follows: vagina/pelvis in 5 of 14 patients, lungs in 8 of 15, intra-abdominal in 4 of 12, and supraclavicular lymph nodes in 1 of 14. One of the four intra-abdominal disseminations was in Group 1 and the other three in Group 2 (p = 0.6). The 5-year vaginal/pelvic control, disease-free survival (DFS), and overall survival (OS) rate was 93% (95% confidence interval [CI] 87–99%), 79% (95% CI 69–89%), and 74% (95% CI 64–85%), respectively. No significant difference in outcome was found between Groups 1 and 2. The 5-year vaginal/pelvic control rate was 97% (95% CI 91–100%) in Group 1 compared with 90% (95% CI 81–99%) in Group 2 (p = 0.2). The 5-year DFS rate was 79% (95% CI 64–95%) in Group 1 vs. 78% (95% CI 65–92%) in Group 2 (p = 0.6), and the 5-year OS rate was 71% (95% CI 55–87%) in Group 1 vs. 79% (95% CI 66–92%) in Group 2 (p = 0.3). The influence on outcome of age, race, comprehensive surgical staging, CSLI, amount of myometrial invasion, cervical involvement, lower uterine segment involvement, and presence of pure PS or CC histologic features was evaluated. On multivariate analysis, only CSLI correlated with poor DFS (p = 0.04; relative risk 3, 95% CI 1–9) and OS (p = 0.02; relative risk 3, 95% CI 1–6).Conclusion: On the basis of the results of this study, no significant difference in outcome exists between patients with Stage I–II endometrial cancer with PS/CC histologic features and those with similar stage disease, but with FIGO Grade 3 endometrioid histologic features. CSLI was the only independent predictor of poor DFS and OS. [Copyright &y& Elsevier]