The widespread use of computerized tomography in evaluating patients with various abdominal complaints gave rise to reports of incidental gastrointestinal luminal wall thickening (GILWT), the clinical significance of which remains uncertain. In order to determine the endoscopic significance of GILWT we reviewed 1609 abdominal and/or pelvic CT scans. Ninety-two patients with GILWT were identified. Patients with obvious clinical cause of this abnormality were excluded from the study. The median age of the patients was 58 years, with no significant difference in gender distribution. The GILWTs were distributed along the GI tract as follows: 24 upper (esophageal, gastric, and duodenum), 13 small intestine (jejunum and ileum), 3 combined small and large intestine, and 52 colon. Fifty of these patients underwent endoscopic evaluation. Six patients (12%) had cancer, all of which involved the colon. The endoscopy was unremarkable in 19 (38%) and revealed a nonmalignant finding in the remaining 25 patients (50%). None of the upper GI or small bowel GILWTs were malignant, while 6 of the 34 colonic GILWTs (18%) were malignant. The mean age of the colonic GILWT group was 59. None of the patients younger than 50 had cancer, while 6 of the 24 older patients (25%) had colon cancer. We conclude that as GILWT is not a common finding and could be the initial presentation of malignancy, particularly when involving the colon in patients older than 50, endoscopic evaluation should be strongly recommended in patients who do not have an alternative diagnosis that can satisfactorily explain GILWT.