Antonio Cassano, Alberto Aquilani and Zlatan Ibrahimovic face Miroslav Klose and Djibril Cissè in Milan-Lazio tonight.
The 2011-12 campaign kicks off at 19.45 UK time at San Siro with two of the contenders for the top spots coming face to face.
The Rossoneri begin the defence of their title, but are without Gianluca Zambrotta, Clarence Seedorf, Robinho, Mathieu Flamini, Philippe Mexes and Taye Taiwo.
Cassano won the race with Alexandre Pato to partner Zlatan Ibrahimovic in attack, while Aquilani makes his Milan debut in midfield.
Lazio also have to make changes, as Lorik Cana, Stefan Radu, Giuseppe Sculli and Marius Stankevicius are sidelined.
There were doubts over Klose after international duty with Germany, but the veteran starts in the centre-forward role supported by Hernanes, Stefano Mauri and fellow Serie A debutant Cissè.
Goalkeeper Federico Marchetti sits out a ban, so Albano Bizzarri takes the gloves.
Milan: Abbiati, Abate, Nesta, Thiago Silva, Antonini; Gattuso, Ambrosini, Aquilani; Boateng; Ibrahimovic, Cassano
Lazio: Bizzarri; Konko, Biava, Dias, Zauri; Ledesma, Brocchi; Cissè, Hernanes, Mauri; Klose