Objective To investigate the clinicopathologic characteristics and relevance of main and minor lesions of synchronous multiple early gastric cancers ( SMEGC) and gastric high grade intraepithelial neoplasia ( GHGIN) . Methods Thirty-two patients with SMEGC or/and GHGIN who were diagnosed and treated with endoscopic submucosal dissection in Nanjing Drum Tower Hospital from July 2012 to September 2016 were enrolled in this study. Their clinicopathologic characteristics were summed up, and the correlation between main and minor lesions on the size, location, endoscopic classification, pathologic type, invasion depth and vascular invasion were analyzed. Results Among the 32 patients, with mean age of 66. 19±7. 46 years, 90. 62％(29/32) were male, 17 cases (53. 3％) had family history of gastric cancer, 25 (78. 13％) had smoking history, and 22 ( 68. 75％) were alcohol users. There were 30 cases ( 93. 75％) and 31 cases ( 96. 88％) with mucosal atrophy and intestinal metaplasia, respectively. The size of main and minor lesions showed a positive correlation (r=0. 4167, P=0. 018). The endoscopic classification of major and minor lesions had no statistical significant consistency ( P=0. 314 ) , but the pathologic type and invasion depth between major and minor lesions demonstrated a moderate significant positive correlation ( P<0. 05 ) . The comparison of location between the main and minor lesions did not show correlation. However, it showed a significant correlation between major lesion which on the upper 1/3 of stomach and minor lesion on the lower 1/3 of stomach ( r=0. 463,P=0. 003) . Further more, when the main lesion was at posterior gastric wall, the minor lesions on lesser curvature were increased, which showed a positive correlation( r=0. 417,P=0. 009) . Conclusion Old-age male with long-term smoking and alcohol history whose lesions combined with surrounding mucosa merger atrophy and intestinal metaplasia are considered as a high risk group in patients with SMEGC or/and GHGIN. Therefore, clinicians must keep high vigilant and make carefully observations on this group of patients during endoscopic examination, and consider the correlation between main and minor lesions to avoid misdiagnosis.