Background: Gastric cancer(GC) is heterogeneous disease, recent years has established a molecular classification and described distribution of molecular subtypes in stomach. However, the clinicopathological difference of gastric cancer between lesser and greater curvature is still unknown. In this study, we investigated the clinicopathological difference of gastric cancer between lesser and greater curvature. Methods: Between January 2010 and August 2014, 1249 consecutive patients with GC located at lesser or greater curvature were treated in our surgery department, the data of demographic, pathological type, differentiation, tumor size, TNM stage, tumor markers, operative methods, complications and follow-up data were analyzed by univariant analysis and Kaplan-Meier analysis retrospectively. Results: We found the tumor size in lesser curvature was larger than in greater curvature (4.95±2.57 vs. 4.43±2.62cm, P=0.034); The patients with gastric cancer in lesser curvature had a higher incidence of total gastrectomy, but a lower incidence of distal gastrectomy than it in greater curvature (60.2% vs. 43.2%, and 34.8% vs. 49.2%, P=0.002); The 5-year survival rate of gastric cancer between the curvatures was not statically significant (62.6±0.02% vs.66.1±0.06%, P=0.496); The rate of EGFR expression in lesser curvature was 40.55%, which was significantly higher than that in greater curvature (25.92%,P=0.024), and the 5-year survival rate in patients with EGFR positive was 50.8±0.06%, which was significantly lower than that in patients with EGFR negative (64.8±0.03%,P=0.021). Conclusions: Our results suggest that the clinicopathological difference of gastric cancer is significant between lesser and greater curvature. Emphasizing the difference contribute to improve outcome of treatment.