The grade of histologic differentiation is one of the most important prognostic factors in patients with endometrial carcinoma and postoperative staging. The aim of this study was to investigate whether 16 alpha-F-18-fluoro-17 beta-estradiol (F-18-FES) and F-18-FDG PET reflect clinicopathologic features in patients with endometrial tumors. Methods: A total of 22 patients with endometrial adenocarcinoma and 9 with endometrial hyperplasia (mean age, 56.0 +/- 15.3 y) underwent F-18-FES PET for estrogen receptor imaging and F-18-FDG PET. Regional values of tracer uptake were evaluated using standardized uptake value (SUV) and the SUV ratio of F-18-FDG to F-18-FES. The accuracy for predicting tumor aggressiveness defined as high-risk carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage >= Ic or histologic grade >= 2), low-risk carcinoma (FIGO stage <= Ib and grade 1), and hyperplasia was compared for each PET parameter using receiver-operating-characteristic (ROC) analysis. The diagnostic accuracy of MRI findings for clinical staging was also compared. Results: Although the SUV for F-18-FDG was significantly lower in endometrial hyperplasia than in carcinoma, a significant difference between high-risk and low-risk carcinoma was observed only in SUV for F-18-FES. High-risk carcinoma showed a significantly greater F-18-FDG-to-F-18-FES ratio (3.6 +/- 2.1) than did low-risk carcinoma (1.3 +/- 0.5, P < 0.01) and hyperplasia (0.3 +/- 0.1, P < 0.005). Low-risk carcinoma showed a significantly higher F-18-FDG-to-F-18-FES ratio than hyperplasia (P < 0.0001). In ROC analysis, the most accurate diagnostic PET parameter for predicting high-risk and low-risk carcinoma was the F-18-FDG-to-F-18-FES ratio. The optimal F-18-FDG/F-18-FES cutoff value of 2.0, determined by ROC analysis, revealed 73% sensitivity, 100% specificity, and 86% accuracy, which was better than the 77% accuracy for MRI. The F-18-FDG-to-F-18-FES ratio of 0.5 yielded a correct diagnosis for carcinoma from hyperplasia with 100% accuracy. Conclusion: Endometrial carcinoma reduces estrogen dependency with accelerated glucose metabolism as it progresses to a higher stage or grade. F-18-FES and F-18-FDG PET studies provide a new index of the F-18-FDG-to-F-18-FES ratio, which is considered the most informative index reflecting tumor aggressiveness. This index will be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial carcinoma.