AIM: To assess the diagnostic accuracy of endoscopic ultrasound (EUS), fluid tumor markers and cytology in distinguishing benign from (pre)malignant pancreatic cystic lesions. METHODS: 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst, were reviewed. EUS, cytology, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis, based on surgical pathology and/or imaging follow-up of at least 12 mo. Cysts were classified as benign (pseudocyst, serous cystadenoma) or malignant/ pre-malignant (mucinous cystic neoplasm). Receiver- operator characteristics (ROC) curve analysis was performed. RESULTS: The mean age was 56 years; 29% were male and median cyst diameter was 3 cm. Final outcome was obtained in 41 (89%) patients. Twenty-three (56%) of these 41 had surgical pathology. Twenty-three (56%) had benign lesions and 18 (44%) had malignant/pre- malignant lesions. Sensitivity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant/premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85%, respectively. The corresponding values for the ROC-derived ideal cutoffswere 75%, 90%, 75%, 90% for CA 19-9 (> 37 U/mL) and 70%, 85%, 79% and 78% for CEA (> 3.1 ng/mL). Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs. CONCLUSION: Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from (pre)malignant pancreatic cystic lesions. AIM: To assess the diagnostic accuracy of endoscopic ultrasound (EUS), fluid tumor markers and cytology in distinguishing benign from (pre) malignant pancreatic cystic lesions. METHODS: 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst , were reviewed. EUS, cytology, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis, based on surgical pathology and / or imaging follow-up of at least 12 mo. Cysts were Results: The mean age was 56 years; 29% were male and median cyst diameter was twenty-three (56%) had benign lesions and 18 (44%) had malignant / pre - malignant lesions. Sensiti vity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant / premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85% respectively. The corresponding values ​​for the ROC-derived ideal cutoffswere 75%, 90%, 75%, 90% for CA 19-9 (> 37 U / mL) and 70%, 85%, 79% and 78% > 3.1 ng / mL). Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs. CONCLUSION: Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from (pre) malignant pancreatic cystic lesions.