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Objective: A high rate of unnecessary thymectomies has been reported. This study aimed to distinguish primary mediastinal lymphomas (PMLs) from thymic epithelial tumors (TETs) by evaluating volumetric and metabolic parameters with 18F-FDG PET/CT.Methods: A total of 136 patients who were pathologically diagnosed with TETs or PMLs were enrolled, and 18F-FDG PET/CT was performed before therapy. Volumetric parameters, including the mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax, were determined and compared between the 2 subtypes. The diagnostic performance of these parameters was evaluated with receiver operating characteristic (ROC) curve analysis.Results: All parameters significantly differed between patients with PMLs and TETs. Patients with lymphomas were younger and had higher SUVmean, SUVmax, TLG, and MTV values than patients with TETs. The MTV and TLG values had similar diagnostic performance. ROC analysis indicated that the areas under the curves of the SUVmean and SUVmax values performed similarly (approximately 0.76) in differentiating patients with PMLs from TETs, and both values were better than the MTV and TLG values.When age was included with the SUVmax in differentiating TETs from PMLs, the AUC was 0.91, and the sensitivity and specificity increased to 80% and 93%, respectively.Conclusions: The SUVmax and volumetric parameters of 18F-FDG PET/CT can be used to distinguish patients with PMLs versus TETs, and thus may aid in preventing unnecessary thymectomies or other invasive operations.