Background: The standard of practice when a superficial lesion was identified during upper GI endoscopy is to take an endoscopic forceps biopsy (EFB) of the lesion. The histopathologic findings then will determine the management plan. Endoscopic submucosal dissection (ESD) enables en-bloc resection for early neoplasms of the gastrointestinal tract and provides an adequate specimen that permits a more reliable histopathologic assessment. The objective of this study was to determine the rate of histopathologic discrepancy between EFB and specimens resected by ESD, and to identify the predisposing risk factors for this discordance. Materials and Methods: This is a retrospective study, enrolling patients with superficial gastric neoplasms that underwent EFB followed by ESD. We divided cases to concordant or discordant group according to the histopathologic diagnosis of EFB and ESD specimens. We also analyzed the features that may have influenced the occurrence of histopathologic discordance and the association between discordant samples of adenocarcinoma and neoplastic invasion to deeper layers. Results: A total of 115 gastric ESD procedures were performed with 84 patients meeting the inclusion criteria. Histopathologic discordance between EFB and ESD specimens were observed in 35.8% of cases (30/84 lesions). The univariant-bivariant analysis and multivariate logistic regression analysis showed that histologic discordance was closely related to the size of the lesions (P=0.028). Conclusion: Histopathologic discrepancy between EFB and ESD specimens may occur in approximately one-third of cases, particularly for lesions over 20 mm, which may lead to crucial delays in gastric cancer precise diagnosis and treatment.