BACKGROUNDGastric ‘indefinite for neoplasm/dysplasia’ (IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management.AIMTo determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions.METHODSIn total, 461 gastric lesions diagnosed via biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection (n = 134), surgery (n = 22), and follow-up endoscopic biopsy (n = 305) were performed to confirm the diagnosis. The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia (60%) or atypical epithelia (40%) at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases.RESULTSFour clinical factors [age ≥ 60 years (2.445, 95%CI: 1.305-4.580, P = 0.005), endoscopic size ≥ 10 mm (3.519, 95%CI: 1.891-6.548, P < 0.001), single lesion (5.702, 95%CI: 2.212-14.696, P < 0.001), and spontaneous bleeding (4.056, 95%CI: 1.792-9.180, P = 0.001)], and two pathologic factors [atypical epithelium (25.575, 95%CI: 11.537-56.695, P < 0.001], and repeated IFND diagnosis [6.022, 95%CI: 1.822-19.909, P = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were 91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change (5.594, 95%CI: 1.458-21.462, P = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review.CONCLUSIONMore than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.