Objective: To evaluate the application of ~(18)F-FDG PET/CT in diagnosis of classic fever of unknown origin. Methods: A total of 27 consecutive patients with classic fever of unknown origin (FUO) (19 men,8 women; aged 24-82 y) underwent ~(18)F-FDG PET/CT scans.The images were interpreted by visual inspection and semiquantitative analysis (standardized uptake value,SUV).Final diagnosis was based on histopathology or clinical follow-up. Results: The cause of FUO was confirmed by followed investigations in 21 of 27 cases after PET/CT scan,including 10 cases of infection,4 of noninfectious inflammation,4 of malignancies and 3 of miscellaneous disorders; and remaining 6 cases were still confirmed FUO.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 100.0;,83.3;,83.3;,100.0; and 96.3;,respectively. Conclusion: For patients with fever of unknown origin,~(18)F-FDG-PET/CT can be a sensitive,reliable imaging modality.It is suggested that ~(18)F-FDG-PET/CT should be considered earlier in detecting the causes of FUO,which is difficultly diagnosed by conventional modalities.