Background and AimThe significance of gastric xanthelasma in relation to gastric disease still remains unclear. We investigated the prevalence and significance of gastric xanthelasma in patients with atrophic gastritis and gastric cancer. MethodsA total of 3238 patients who underwent endoscopic examinations of the upper gastrointestinal tract were enrolled. We retrospectively investigated the presence of gastric xanthelasma, the severity of gastric atrophy, and the presence of gastric cancer, and examined the relationship between gastric xanthelasma and various clinicopathological features. ResultsGastric xanthelasma was detected in 249 (7.7%) of the 3238 patients and was significantly associated with age 65 years, male gender, open-type atrophy, and the presence of gastric cancer (P<0.0001, P=0.0002, P<0.0001 and P<0.0001, respectively). Multivariate analysis revealed that the presence of gastric cancer was independently related to the presence of gastric xanthelasma (odds ratio 6.19 [3.95-9.70], P<0.0001). Age/sex/atrophy-matched control analysis demonstrated that the presence of gastric xanthelasma was significantly associated with the presence of gastric cancer (P<0.0001). Moreover, the presence of xanthelasma in the upper region of the stomach was significantly associated with gastric cancer (P=0.002). Gastric xanthelasma was observed in 50 (47.6%) of 105 patients with gastric cancer. ConclusionGastric xanthelasma may serve as a warning sign for the presence of gastric cancer.