Pre-operative assessment of a potentially resectable peri-pancreatic mass by computed tomography (CT) is widely used, but often of limited value for lesions less than 5 cm. ERCP is frequently used to evaluate those patients with associated obstructive jaundice. To determine the clinical effectiveness of endoscopic ultrasonography (EUS), patients with pancreatobiliary lesions of less than 5 cm with or without obstructive jaundice were evaluated. CT scan, ERCP, and EUS were performed on 60 patients with a peri-pancreatic mass and/or obstructive jaundice. The results of the examinations were compared with respect to detection of an abnormality, diagnosis, and prediction of resectability. ERCP and EUS were the most sensitive and specific in detecting an abnormality of the pancreatobiliary system. The accuracy of EUS compared with the accuracy of the combination of CT scan with ERCP was significantly higher for the evaluation of the specific type and extent of pancreatobiliary disease (73% vs. 30%, p < 0.001) and prediction of resectability (75% vs. 38%, p < 0.05). EUS aided patient management in 75% by providing more details about the disease, and changed management in 32% by making a diagnosis or changing an incorrect diagnosis. EUS represents a significant advance in the evaluation and clinical management of pancreatobiliary disease.