Focal 2-deoxy-2[fluorine-18]fluoro-D-glucose (FDG) uptake on positron emission tomography (PET) in a pancreatic mass has been reported as a specific finding for pancreatic carcinoma. Inflammatory conditions of the pancreas and associated clinical circumstances yielding similar findings have not yet been fully defined. Among 42 patients studied by attenuation-corrected FDG PET for pancreatic disease, 12 with focal FDG uptake in the pancreas were identified as having no underlying neoplasm based on surgical findings, biopsy results, and long term clinical and imaging follow up. Focal FDG accumulation in the pancreas with standardized uptake values ranging from 3.4 to 11.2 on FDG PET was ultimately found to be related to inflammation rather than neoplasm. This occurred in pancreatic masses in which clinical and laboratory evidence of acute pancreatitis was equivocal or entirely lacking, as well as in the setting of acute pancreatitis and after recovery from acute pancreatitis. Inflammation can give rise to focal FDG uptake in the same intensity range as pancreatic neoplasm, even when clinical, laboratory and computed tomographic findings suggestive of an inflammatory etiology are equivocal or absent.