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Intracranial gliomas and lymphomas may share similar radiological manifestations, while the treatment strategies for them are different. The aim of the study was to investigate the diagnostic value of fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission computed tomography (PET) for differentiation of multicentric gliomas and intracranial multiple diffuse large B-cell lymphomas (DLBCLs) as a study of diagnostic accuracy.A total of 32 patients with multiple intracranial tumors visualized on contrast-enhanced magnetic resonance imaging (MRI) were retrospectively evaluated. Histopathological findings confirmed multicentric gliomas and multiple DLBCLs in 17 and 15 patients, respectively. All patients underwent 18F-FDG PET with or without 11C-methionine PET. Maximum standardized uptake values (SUVmax) and tumor-to-normal tissue (T/N) ratios were compared between the 2 tumors. The diagnostic value of 18F-FDG PET for differentiating multicentric gliomas from multiple DLBCLs was evaluated by receiver operating characteristic (ROC) analysis.The SUVmax of multiple DLBCLs was significantly higher than that of multicentric gliomas (P = .009). However, the percentage of maximum difference-value of SUVmax (or T/N ratio) of multiple DLBCLs was significant lower than that of multicentric gliomas (P < .001). The ROC curve demonstrated that the percentage of maximum difference-value of SUVmax (or T/N ratio) on 18F-FDG PET images could effectively differentiate multicentric gliomas from multiple DLBCLs, with a cut-off value of 44.4%, sensitivity of 64.7%, and specificity of 100% (P < .001).Percentage of maximum difference-value of SUVmax (or T/N ratio) on 18F-FDG PET images might be a potential indicator for distinguishing multicentric gliomas from intracranial multiple DLBCLs, which might help determine the treatment strategy.