Champions Inter now have an 11-point advantage over third-placed Milan with 14 games to go and lead Juventus by nine after Claudio Ranieri's side drew 1-1 at home to Sampdoria.
PHOTOS: Inter 2-1 Milan
Adriano broke the deadlock at an electric San Siro on 28 minutes when he diverted in Maicon's cross, but replays showed the Brazil striker had used his arm.
Midfielder Dejan Stankovic extended the lead on 42 minutes when he rifled in after Zlatan Ibrahimovic's knockdown.
Alexandre Pato pulled one back 20 minutes from time when he tapped in Marek Jankulovski's cross and Milan then piled on the pressure with substitute Filippo Inzaghi being flagged offside when he thought he had grabbed an equaliser.
Milan, who won the season's earlier derby 1-0, had much of the play in the first half but striker Pato was constantly isolated on his own up front with Kaka missing through injury.
Media reports have said Milan coach Carlo Ancelotti, Serie A's longest serving manager having been appointed in 2001, could be sacked if they fail to win the league this term.
Amauri's brave diving header midway through the second half levelled the scores after a teasing cross from substitute Sebastian Giovinco.
Cassano's deflected cross struck the post for Samp.
AS Roma's good run ended with a 3-0 defeat at Atalanta, who beat Inter 3-1 in Bergamo last month.
