Background: Increasing use of 18F-FDG PET/CT in cancer patients, has led to more common detection of 18F-FDG uptake in the gastrointestinal tract (GIT). Aims: The objective of this study was to assess 18F-FDG uptake in incidental and known GIT malignancy. Methods: A total of 6500 patients followed-up in a single and tertiary center between January 2010 and September 2016 were retrospectively reviewed. Of 2850 patients assessed with 18FDG-PET/CT, known GIT malignancy and 18F-FDG uptake cases during follow-up were included in the study. Results: Of 658 patients with 18F-FDG uptake, 150 patients who underwent endoscopy were included in the study. Seventy-seven of these patients had known GIT malignancy and 73 had incidental 18F-FDG uptake. Among these 73 patients; 7 (9.6%) had malignancy, 20 (27,2%) adenoma and 24 (32.9%) inflammation that were confirmed. Endoscopy was normal in 22 (30.2%) patients. One hundred forty-three (95.3%) patients had focal and 7 (4.7%) had diffuse uptake. While no malignancy was detected in patients with diffuse uptake, 58.7% (84/143) of the patients with focal uptake presented malignancy. Mean the standardized uptake value (SUV) max values were found as 15.0 ± 10.6 (range, 3.8–56.5) in malignant disease, 10.2 ± 4.3 (range, 2.4-19.7) in adenoma, 7.3 ± 3.6 (range, 3.6–18.7) in inflammation, and 9.8 ± 4.2 (range, 3.8–19.9) in normal endoscopy groups (p < 0.001, rho = 0.378). Conclusion: Although this study demonstrated high probability of malignant disease with increased 18F-FDG uptake in the GIT, it would be a more appropriate approach to confirm all patients with 18F-FDG uptake through endoscopy as SUVmax values vary in a wide range.