AIM To evaluate the clinical impact of confocal laser endomicroscopy(CLE) in the diagnosis and management of patients with an uncertain diagnosis.METHODS A retrospective chart review was performed.Patients who underwent CLE between November 2013 and October 2015 and exhibited a poor correlation between endoscopic and histological findings were included.Baseline characteristics,indications,previous diagnostic studies,findings at the time of CLE,clinical management and histological results were analyzed.Interventions based on CLE findings were also analyzed.We compared the diagnostic accuracy of CLE and target biopsies of surgical specimens.RESULTS A total of 144 patients were included.Of these,51%(74/144) were female.The mean age was 51 years old.In all,41/144(28.4%) lesions were neoplastic(13 bile duct,10 gastric,8 esophageal,6 colonic,1 duodenal,1 rectal,1 ampulloma and 1 pancreatic).The sensitivity,specificity,positive predictive value,negative predictive value,and observed agreement when CLE was used to detect N-lesions were 85.37%,87.38%,72.92%,93.75% and 86.81%,respectively.Cohen’s Kappa was 69.20%,thus indicating good agreement.Changes in management were observed in 54% of the cases.CONCLUSION CLE is a new diagnostic tool that has a significant clinical impact on the diagnosis and treatment of patients with uncertain diagnosis. AIM To evaluate the clinical impact of confocal laser endomicroscopy (CLE) in the diagnosis and management of patients with an uncertain diagnosis. METHODS A retrospective chart review was performed. Patients who underwent CLE between November 2013 and October 2015 and exhibited a poor correlation between endoscopic and histological findings were included.Baseline characteristics, indications, previous diagnostic studies, findings at the time of CLE, clinical management and histological results were analyzed.Interventions based on CLE findings were also analyzed. We compared the diagnostic accuracy of CLE and target biopsies of 51% (74/144) were female. The mean age was 51 years old. All in 41/144 (28.4%) lesions were neoplastic (13 bile duct , 10 gastric, 8 esophageal, 6 colonic, 1 duodenal, 1 rectal, 1 ampulloma and 1 pancreatic). The sensitivity, specificity, positive predictive value, negative predictive value, and reduced agreement When CLE was used to detect N-lesions were 85.37%, 87.38%, 72.92%, 93.75% and 86.81%, respectively. Cohen’s Kappa was 69.20%, thus indicating good agreement. Changes in management were observed in 54% of the cases. CONCLUSION CLE is a new diagnostic tool that has a significant clinical impact on the diagnosis and treatment of patients with uncertain diagnosis.