The differential diagnosis between benign and malignant pancreatic cystic lesions may be very difficult. We recently found that F-18-fluorodeoxyglucose positron emission tomography (18-FDG PET) was useful for the preoperative work-up of pancreatic cystic lesions. This study was undertaken to confirm these results. From February 2000 to July 2003, 50 patients with a pancreatic cystic lesion were prospectively investigated with 18-FDG PET in addition to helical computed tomography (CT) and, in some instances, magnetic resonance imaging (MRI). The validation of diagnosis was based on pathologic findings after surgery (n=31), percutaneous biopsy (n=4), and according to follow-up in 15 patients. The 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value (SUV). The accuracy of FDG PET and CT was determined for preoperative diagnosis of malignant cystic lesions. Seventeen patients had malignant cystic lesions. Sixteen (94%) showed increased 18-FDG uptake (SUV>2.5), including two patients with carcinoma in situ. Eleven patients (65%) were correctly identified as having malignancy by CT. Thirty-three patients had benign tumors: two patients showed increased 18-FDG uptake, and four patients showed CT findings of malignancy. Sensitivity, specificity, positive and negative predictive value, and accuracy of 18-FDG PET and CT in detecting malignant tumors were 94%, 94%, 89%, 97%, and 94% and 65%, 88%, 73%, 83%, and 80%, respectively. 18-FDG PET is accurate in identifying malignant pancreatic cystic lesions and should be used in combination with CT in the preoperative evaluation of patients with pancreatic cystic lesions. A negative result with 18-FDG PET may avoid unnecessary operation in asymptomatic or high-risk patients.