A snout of a large-sized mosasaur from the Upper Cretaceous pelagic-turbiditic deposits of the Argille Scagliose Complex of Northern Italy is described. Nannofossil assemblages from the immediately overlying strata belong to the late but not latest Campanian calcareous nannofossil standard zone CC22, based on the presence of Uniplanarius trifidus and Eiffellithus eximius. The specimen includes a broken premaxilla, the anterior part of the maxillae and dentaries in articulation: preserved teeth show distinctive characters previously unreported in other mosasaurs. Although the marginal teeth show a posterior migration of the labial carina along the jaw length – diagnostic of derived mosasaurines – they are unusual in the combination of features, including anteriormost teeth with asteroid cross section followed by teeth with crowns twisted labioposteriorly from one-third to one-half of their height toward the apices. A comparison between the new specimen and Mosasaurus hoffmanni skulls suggests an estimated skull length comparable with some of the largest known mosasaurids. Consequently, the new specimen represents the largest mosasaur and the largest fossil reptile found in Italy to date. Several lines of dental evidence also support the interpretation of the Italian mosasaur as a macrophagous generalist predator. Paleogeographic reconstruction for the Argille Scagliose Complex as well as the occurrence of typical low- to mid-latitude nannofossils support a southern Tethyan margin affinity of the taxon.