 After some occasional participations to stage plays and films, he had his breakout with the role of Tarcisio in the 1995 crime film "Palermo - Milan One Way" by Claudio Fragasso.In 1997 he got his first leading role in the sleeper box office hit "We All Fall Down".Mastandrea won the David di Donatello for Best Actor for his role in "The First Beautiful Thing" in 2010.