He achieved stardom following his lead role in Daniele Luchetti's My Brother Is an Only Child (2007), for which he won his first David di Donatello for Best Actor. He won the award for Best Actor at the 2010 Cannes Film Festival for Luchetti's La Nostra Vita (tied with Javier Bardem for Biutiful) and at the 2020 Berlin Film Festival for Volevo Nascondermi, portraying painter Antonio Ligabue.

Subsequent starring roles include Tutta La Vita Davanti (2008), Diaz: Don't Clean Up This Blood (2012), Il Giovane Favoloso (2014), Suburra (2015), The Man Without Gravity (2019), Bad Tales (2020) and Rose Island (2020). Outside of Italy he appeared in the Abel Ferrara's Mary (2005), and Nine (2009), opposite Daniel Day-Lewis.