OBJECTIVE: The purpose of this study was to assess the value of 2-[F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) in the primary staging of high-risk endometrial cancer patients. METHODS: This retrospective study was conducted on 32 consecutive patients with histological diagnosis of primary high-risk endometrial cancer, who underwent PET/CT with [F]FDG in addition to conventional clinical and instrumental staging procedures. After surgery, [F]FDG PET/CT findings were correlated with pathological findings on a patient-by-patient basis. The diagnostic accuracy of [F]FDG PET/CT for primary cancer detection, lymph nodal involvement and distant metastases was assessed. RESULTS: [F]FDG PET/CT could correctly detect primary tumor in 29 of the 32 high-risk patients, with a sensitivity of 90.6%. The overall [F]FDG PET/CT patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 57.1, 100.0, 100.0, 86.4, and 88.5%, respectively, for revealing lymph nodal neoplastic involvement, and 100.0, 96.0, 87.5, 100.0, 96.9%, respectively, for detecting distant metastases. In particular, while the suspicion of distant metastases was documented by conventional imaging in only two patients, [F]FDG PET/CT correctly identified metastatic lesions in seven patients (21.9% of cases). CONCLUSION: The major benefit provided in high-grade tumor patients by the use of [F]FDG PET/CT in the primary staging of endometrial cancer is its ability to accurately detect distant metastases in the abdomen and extra-abdominal regions. [F]FDG PET/CT adds relevant information that may influence patient management.