To evaluate the application of (18)F-FDG PET/CT in diagnosis of classic fever of unknown origin. 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. 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. 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.