AIMS. The aim of this study was to evaluate the leading causes of discrepancies between imaging studies [contrast enhanced ultrasound (CEUS) and contrast enhanced computer tomography (CECT)] diagnosis and histology in patients presenting to a tertiary referral center with previously detected pancreatic masses by standard abdominal ultrasound. METHODS. We performed a prospective longitudinal observational study on 76 patients with pancreatic masses: 57 (75%) patients with solid pancreatic tumors and 19 (25%) patients with cystic and mixed pancreatic masses. For each tumor the CEUS and CECT features were analyzed and compared with the final histological diagnosis. RESULTS. Testing the performance of CEUS and CECT in evaluating the benign or malignant etiology of pancreatic masses, we obtained a probability of 82% for CEUS and of 83% for CECT, for a randomly selected individual from the pancreatic tumor group to have an imaging result indicating suspicion for malignancy. We obtained discordances with the histopathological diagnosis in 25 (32.89%) patients for CEUS and in 23 (30.26%) patients for CECT. In multiple regression analysis, two variables independently influenced the discordance between the two imaging methods and histological conclusion: enhancement pattern and tumor nature (solid vs. cystic). CONCLUSIONS.CEUS and CECT showed a good diagnostic performance in differentiating benign from malignant pancreatic tumors. Enhancement pattern and tumor nature (solid vs. cystic) are independent confounders between imaging and histological diagnosis.