[Abstract] Objective To investigate the risk factors of pathological discrepancy between biopsy and excisional specimen from gastric low-grade intraepithelial neoplasia (LGIN) and early gastric cancer (EGC). Methods A retrospective analysis was conducted on the data of 235 patients who underwent endoscopic submucosal dissection or surgical resection and diagnosed as LGIN or EGC (including high-grade intraepithelial neoplasia) by postoperative pathology. Patients were grouped by whether there was significant pathological discrepancy between biopsy and excisional specimen. Univariate and multivariate analyses were used to analyze the risk factors for significant pathological discrepancy. Results Significant pathological discrepancy occurred in 33 cases (14%). Univariate analysis showed that protruding lesion, non-reddish surface, without erosion or ulcer, diffused pathological type and number of biopsy were related to the pathological discrepancy (all P<0.05). Multivariate analysis suggested that small number of biopsy blocks (OR=0.574, 95%CI: 0.363-0.908, P=0.018) was an independent risk factor for significant pathological discrepancy. Conclusion The pathological discrepancy between biopsy and excisional specimen from gastric LGIN and EGC are common. Multiple biopsies can improve the accuracy of biopsy and reduce the occurrence of pathological discrepancy with excisional specimen.