Leptin is an adipocyte-derived hormone that regulates body fat stores and feeding behavior. The presence of leptin in stomach epithelium was recently demonstrated in the rat and humans, and gastric leptin has been linked to the control of meal size, local inflammatory responses, and paracrine and autocrine functions through leptin receptors in the stomach. We compared the expression patterns of leptin and of the long variant of the leptin receptor (Ob-Rb) between areas with non-ulcerated mucosa and with hyperplastic polyps, adenoma, or adenocarcinoma to evaluate the expression relative to different disease states. Leptin and Ob-Rb were expressed in hyperplastic polyps, adenoma, and adenocarcinoma. In the gastric adenocarcinoma, leptin was expressed significantly less in the poorly differentiated and diffuse-type groups than in the well-differentiated and moderately differentiated groups or in the intestinal type. Based upon our findings, we suggest the possibility that leptin expression can have a pathophysiologic role about the differentiation or growth pattern of gastric adenocarcinoma. A further series of experiments is necessary to elucidate the pathophysiological role of leptin in the differentiation of gastric adenocarcinoma.