BACKGROUND: Endoscopic forceps biopsy is the primary method for obtaining mucosal tissues, but can lead to false negatives. AIMS: To assess the agreement between endoscopic biopsies and submucosal dissection specimens in esophageal and gastric epithelial lesions and to identify factors associated. METHODS: Cross-sectional study using data from the Spanish national multicenter endoscopic submucosal dissection register. Patients, lesions and technical characteristics were prospectively collected. Prognostic factors for discrepancies were analyzed. RESULTS: 604 endoscopic submucosal dissection with previous biopsies were performed between January 2016 and December 2023 across 32 centers. 48.7% presented disagreement between biopsies and endoscopic submucosal dissection
specifically, 40.4% were underestimated by endoscopic biopsy. Carcinoma was detected in 270 endoscopic submucosal dissection specimens, with 54.8% not suspected on the initial biopsy. The carcinomas already diagnosed with the biopsy presented more submucosal and lymphovascular invasion. Notably, a larger lesion (≥ 22 mm) was a significant predictor for histological upstaging. CONCLUSIONS: The high rate of disagreement between endoscopic forceps biopsy and endoscopic submucosal dissection highlights biopsies limitations in accurately diagnosing esophageal and gastric epithelial lesions. In this setting, endoscopic submucosal dissection should be used not only as a treatment option, but also as a valuable diagnostic tool.