Abstract: Background Carcinoma of unknown primary (CUP) encompasses a heterogeneous group of tumors with varying clinical features. The management of patients of CUP remains a clinical challenge. The purpose of this study was to evaluate the clinical applications of integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) information in patients with CUP,including detecting the occult primary tumor and effecting on disease therapy.Methods One hundred and forty-nine patients with histologically-proven metastases of CUP were included. For all patients,the conventional diagnostic work-up was unsuccessful in localizing the primary site. Whole-body PET/CT images were obtained approximately 60 minutes after intravenous injection of 350-425 MBq of 18F-FDG.Results In 24.8% of patients,FDG PET/CT detected primary tumors that were not apparent after conventional workup.In this group of patients,the overall sensitivity,specificity,and accuracy rates of FDG PET/CT in detecting unknown primary tumors were 86.0%,87.7%,and 87.2%,respectively. FDG PET/CT imaging also led to the detection of previously unrecognized metastases in 29.5% of patients. Forty-seven (31.5%,47 of 149) patients underwent a change in therapeutic management.Conclusions FDG PET/CT is a valuable tool in patients with CUP,because it assisted in detecting unknown primary tumors and previously unrecognized distant metastases,and optimized the mangement of these patients.