AIM: To assess the utility of contrast-enhanced ultrasonography (CEUS) with a second-generation contrast medium in the differential diagnosis between mass-forming pancreatitis and pancreatic carcinoma.METHODS: From our radio-pathology database, we retrieved all the patients affected by mass-forming pancreatitis or pancreatic carcinoma who underwent CEUS. We evaluated the results of CEUS in the study of the 173 pancreatic masses considering the possibilities of a differential diagnosis between mass-forming pancreatitis and pancreatic tumor by identifying the "parenchymographic" enhancement during the dynamic phase of CEUS, which was considered diagnostic for mass-forming pancreatitis.RESULTS: At CEUS, 94% of the mass-forming pancreatitis showed intralesional parenchymography.CEUS allowed diagnosis of mass-forming pancreatitis with sensitivity of 88.6%, specificity of 97.8%,positive predictive value of 91.2%, negative predictive value of 97.1%, and overall accuracy of 96%. CEUS significantly increased the diagnostic confidence in the differential diagnosis between mass-forming pancreatitis and pancreatic carcinoma, with receiver operating characteristic curve areas from 0.557 (P = 0.1608) for baseline US to 0.956 (P ＜ 0.0001) for CEUS.CONCLUSION: CEUS allowed diagnosis of massforming pancreatitis with diagnostic accuracy of 96%. CEUS significantly increases the diagnostic confidence with respect to basal US in discerning mass-forming pancreatitis from pancreatic neoplasm.