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To evaluate the performance characteristics of endoscopic ultrasonography (EUS) compared with computed tomography (CT) and magnetic resonance imaging (MRI) and determine the incremental diagnostic yield and accuracy of EUS with or without fine needle aspiration (FNA) over CT and MRI for prediction of neoplastic pancreatic cysts.The EUS database was queried for procedures performed for pancreatic cysts between March 2006 and January 2010. Cystic pancreatic ductal adenocarcinoma, cystic pancreatic neuroendocrine tumor, mucinous cystic neoplasm, intraductal papillary neoplasm, and solid pseudopapillary neoplasm were categorized as neoplastic; pseudocysts and serous cysts were designated as nonneoplastic/low risk.Final diagnoses were established by surgery in 154 patients (mucinous cystic neoplasm/intraductal papillary neoplasm [69.4%], pancreatic neuroendocrine tumor [10%], pancreatic ductal adenocarcinoma [6.4%], solid pseudopapillary neoplasm [0.6%], nonneoplastic/low risk [13.6%]). Endoscopic ultrasonography with or without FNA was superior to CT and MRI in accurately classifying a cyst as neoplastic (P < 0.0001). After CT and MRI, EUS increased the rate of correctly predicting neoplastic cysts in 43 (36%) and 27 (54%) additional cases, respectively.The incremental increase in diagnostic yield of EUS and fluid analysis over CT and MRI for prediction of a neoplastic cyst is 36% and 54%, respectively. The addition of EUS-FNA to abdominal imaging significantly increases overall accuracy for diagnosis of neoplastic pancreatic cysts.