Introduction: The third most common malignancy worldwide is Gastric cancer. Patients with upper Gastrointestinal alarm symptoms are suspected of having upper gastrointestinal (GI) malignancy; however, the true value of alarm symptoms in predicting an underlying malignancy is uncertain.The aim of the present study was to determine the diagnostic accuracy of alarm symptoms in predicting upper GI malignancy by reviewing the endoscopic findings of 3453 Isfahanian patients that refer to a private GI clinic in Isfahan, Iran.Methods: A cross-sectional retrospective analysis of collected data was conducted in a single tertiary medical centre. Consecutive patients who underwent esophagogastroduodenoscopy (EGD) for upper GI symptoms in June 2009 to January 2015 were enrolled. The data including gender, age, symptoms, and endoscopic and pathological findings were analysed. Logistic regression models were used to estimate the diagnostic value of each variable in combination with others. The main outcome measure was the diagnostic accuracy of individual alarm feature.Results: A total of3453 patients were included in the final analysis, of whom 78 (2.25%) had upper GI malignancy. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated having histology as the gold standard. Odds ratio (OR), and their related 95% confidence intervals for each individual alarm symptom was measured. Univariate and multivariate logistic regression models were used. Using the area under the receiver operating characteristic (ROC) curve and AUC and its 95% confidence intervals were used to evaluate the capability of the model. AUC for diagnostic value were 0.846 that was significant.Conclusion: Our analysis showed that PPV of dysphagia & weight loss in age more than 50 are strong predictors of cancer. The other variables such as GIB, anorexia, vomiting, Familial history are weaker predictors for malignancy.