Abstract Background and study aim: Duodenal mucosal lesions are usually difficult to diagnose. White light endoscopy(WLE) ‎generally does not visualize the duodenal villous patterns properly and miss small ‎elevated lesions, which result in an inaccurate diagnosis. We aimed to assess the ‎diagnostic accuracy of I-scan technology for evaluation and histological confirmation of ‎mucosal lesions in the duodenum and its role in biopsy targeting‎. Patients and Method: ‎This was a single center, cross-sectional study. Patients with any indication for ‎duodenal mucosa histological examination on conventional white light endoscopy WLE ‎and I Scan imaging were included. A definitive diagnosis was determined by ‎histopathology examination of the biopsied specimen.‎ Results: In our study 41 patients were included (25 males, 16 females, mean age 39.9 years). ‎The criterion-related validity of I-scan as a diagnostic test was 91.9% sensitivity, 75% ‎specificity, 97.1% PPV and 50% NPV compared to white light endoscopy , which ‎achieved 67.6% sensitivity, 75% specificity, 96% PPV and 20% NPV. I-scan achieved ‎‎95.1% accuracy, 97% specificity, 75% sensitivity in the diagnosis of celiac disease and ‎detection of duodenal villous atrophy compared to WLE, which achieved 92.7% ‎accuracy, 100% specificity, 25% sensitivity. There was a significant association ‎between disease diagnosis by I-scan and presenting by abdominal pain (p < 0.026)‎‎. Conclusion: I-scan represents a simple technique that helps in the diagnosis of duodenal mucosal ‎lesions with high sensitivity, specificity and reduces false negative diagnosis; especially ‎in patients who had abdominal pain‎‎‎.