We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET) and hybrid PET-computed tomography (CT) scans with [F-18]fluorodeoxyglucose (FDG) in the imaging evaluation of patients with known or suspected recurrent and metastatic cholangiocarcinoma. The study group included 24 patients (13 males and 11 females; age range, 34-75 years) with known or suspected recurrent and metastatic cholangiocarcinoma. We performed 8 dedicated PET scans (Siemens 953/A, Knoxville, Tenn) in 8 patients and 24 hybrid PET-CT scans (Siemens Biograph, Knoxville, Tenn) in 16 patients. Four patients underwent both pretreatment and posttreatment scans. Nonenhanced CT transmission scans were obtained for attenuation correction after administration of oral contrast material. PET images were obtained 60 minutes after the intravenous administration of 15 mCi (555 MBq) FDG. Prior treatments included surgery alone in 12 patients, surgery and chemotherapy in 6 patients, and surgery and combined chemoradiation therapy in 6 patients. Diagnostic validation was conducted through clinical and radiologic follow-up (2 months to 8 years). PET and CT were concordant in 18 patients. PET-CT correctly localized a hypermetabolic metastatic lesion in the anterior subdiaphragmatic fat instead of within the liver and was falsely negative in intrahepatic infiltrating type cholangiocarcinoma. PET was discordant with CT in 6 patients. PET was negative in an enlarged right cardiophrenic lymph node on CT, which remained stable for 1 year. In 1 patient, PET-CT scan showed hypermetabolic peritoneal disease in the right paracolic gutter without definite corresponding structural abnormalities, which was subsequently confirmed on a follow-up PET-CT scan performed 6 months after the initial study, at which time peritoneal nodular thickening was evident on concurrent CT. PET-CT documented the progression of locally recurrent and metastatic disease in another patient based on interval appearance of several new hypermetabolic lesions and significant increase in the standardized uptake values of the known lesions despite little interval change in the size and morphologic character of lesions on concurrent CT. It was also helpful in excluding metabolically active disease in patients with contrast enhancement at either surgical margin of hepatic resection site or focally within hepatic parenchyma and in an osseous lesion. Overall, based on the clinically relevant patient basis for detection of recurrent and metastatic cholangiocarcinoma, the sensitivity and specificity of PET (alone and combined with CT) were 94% and 100% and, for CT alone, were 82% and 43%, respectively. FDG PET and PET-CT are useful in the imaging evaluation of patients with cholangiocarcinoma (except for infiltrating type) for detection of recurrent and metastatic disease and for assessment of treatment response. In particular, the combined structural and metabolic information of PET-CT enhances the diagnostic confidence in lesion characterization.