PURPOSE: To evaluate the clinical usefulness of the 18F 2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) scan in the diagnosis of the ampulla of Vater cancer. MATERIALS AND METHODS: CT images of 39 patients with ampulla of Vater cancer were reviewed regarding the lesion size, location, and bile or pancreatic duct dilatation. The patients were divided into three groups according to the lesion visibility on CT (Group A: visible mass, Group B: no visible mass but prominent ampulla, Group C: no visible lesion). Standardized uptake value (SUV) was measured on PET scan and the detection rate on PET images was comparable with that of CT images. RESULTS: Twenty-four patients (61.5%) were classified as Group A, 11 (28.2%) as Group B and 4 (10.3%) as Group C. All of Group A, 10 (90.9%) of Group B and 3 (75.0%) of Group C showed biliary dilatation. Pancreatic duct dilatation was shown in 18 (75.0%) of Group A, 9 (81.8%) of Group B, and 1 (25.0%) of Group C. The average of SUV of all patients was 5.90 +/- 3.1. Most (94.9%) of all patients showed high FDG uptake over 2.5 with 93.9% in Group B and C. CONCLUSION: 18F-FDG PET scan was use for the detection of ampulla of Vater cancer, even though the lesion was invisible on CT.