The most widely used system for grading of endometrial carcinoma is the International Federation of Gynecology and Obstetrics (FIGO) grading system. This grading system requires evaluation of histologic features that are difficult to assess reproducibly. Two hundred and two cases of endometrial carcinoma, treated by hysterectomy, were retrieved from the archives of Vancouver General Hospital (1983-1998). For each tumor, the architectural pattern, nuclear grade, and mitotic index were assessed. The tumor architectural pattern, nuclear grade, and mitotic index were significant predictors of patient outcome (P < 0.0001 for each, by univariate analysis). There were no prognostic differences between patients having predominantly solid versus papillary tumors, or tumors with mild versus moderate nuclear atypia. The tumors were then classified into high and low grade based on assessment of these three features. The presence of at least two criteria of these three: 1) predominantly papillary or solid growth pattern, 2) mitotic index > or =6/10 high power fields, or 3) severe nuclear atypia, resulted in a tumor being considered high grade. Low-grade tumors satisfied at most one of those criteria. The proposed grading system was found to be an independent predictor of patient outcome when patient survival was adjusted for FIGO stage, patient age, and tumor cell type. It also had more prognostic power than other grading systems tested when it was applied to all tumors, regardless of their cell type; however, the FIGO grading system was superior for prognostication when only carcinomas of endometrioid type were considered. With the FIGO grading system, no significant difference in survival was observed between patients with grade 1 and grade 2 tumors. Combining FIGO grades 1 and 2 results in a binary system (grades 1 and 2 vs. grade 3) that was the most prognostically significant grading system tested, with the additional advantages of being highly reproducible and familiar to practicing pathologists.