Background: Previous studies have suggested that malignant cystic lesions of the pancreas can be reliably distinguished from benign cysts with whole body positron-emission tomography (PET). Methods: We reviewed the Department of Surgery pancreatic cyst database to identify patients who had undergone whole body PET imaging for a cystic lesion of the pancreas between January 1997 and May 2005. A total of 68 patients were identified who had undergone F18 fluorodeoxyglucose (FDG) whole body PET. Patient, cyst, operative, radiographic, and PET imaging characteristics were reviewed. Results: Operative resection was performed in 21 patients (31%), and 47 patients were managed with radiographic follow-up. The average diameter of the cystic lesions was 2.7 cm (0.6 to 15.0 cm), and 66% were discovered incidentally. FDG-avid lesions were identified in eight of the 68 patients (12%), and the average SUV of positive studies was 4.6 (range, 1.9 - 8.0). Within the resected group of patients, four of seven patients (57%) with either in situ or invasive malignancy (adenocarcinoma: 3/5; papillary mucinous carcinoma: 1/2) had a positive PET scan (mean SUV: 5.9; range 2.5 - 8.0). Positive PET scans were obtained in two of 14 patients (14%) who underwent resection for a benign lesion (serous cystadenoma 1/5, benign or borderline IPMN 0/3, mucinous cystadenoma 0/2, or pseudocyst 1/4). Within the group of 47 patients being followed radiographically, two patients (4.3%) had FDG-avid lesions. These two patients had lesions with maximum SUV’s of 1.9 and 5.0, and have been followed radiographically without significant change for 15 and 11 months respectively. Within the group of 21 resected patients, the sensitivity of whole body PET imaging for identifying malignant pathology was 57%, and the specificity was 86%. Conclusions: In this study, whole body FDG PET imaging had a sensitivity of 57% and a specificity of 86% for identifying in situ or invasive histologies. Regional pancreatic PET imaging, or the use of targeted agents, may improve the sensitivity and specificity of PET.