Patrick Cutrone and Davide Calabria scored for the visitors to secure all three points for Gennaro Gattuso's side, on a disappointing night for the Giallorossi faithful.
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Roma arguably had the better of the first half - Cengiz Under and Diego Perotti both forcing Gianluigi Donnarumma into saves - but it was Cutrone who changed the course of the game when he prodded home Suso's cross three minutes into the second half.
Calabria then broke the offside trap to effectively decide the game with 15 minutes remaining.
Patrik Schick made his third league start for the Giallorossi, replacing Edin Dzeko as the main striker in Eusebio Di Francesco's formation.
Elsewhere, Bruno Peres came in at right-back - while a three-man midfield of Lorenzo Pellegrini, Kevin Strootman and Radja Nainggolan meant the latter midfielder also took the captain's armband.
5' - Cengiz forces the first save of the match as Donnarumma tips the in-form forward's low drive around the post.
10' - Perotti flashes a powerful shot at goal that Donnarumma saves and gathers.
23' - Schick meets Kolarov's free-kick and forces Donnarumma into a smart stop... before the linesman's flag goes up for offside.
34' - Big claims for a penalty from Lorenzo Pellegrini, but the referee waves it away.
38' - Pellegrini goes for goal from outside the box but he drags his shot wide of the far post as Donnarumma watches it past.
40' - Schick lifts the crowd with a lovely little turn to beat Calabria and Biglia, but Bonucci comes across to make the covering tackle inside the box.
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48' - Goal. Milan take the lead, as Cutrone flicks home Suso's inswinging cross. 0-1.
51' - Almost an immediate response from the hosts. Schick creates space with some crisp footwork on the edge of the box, but Perotti's shot is low and wide.
54' - Alisson tips over Kessie's dipping long-range strike as Milan counter dangerously after a spell of Roma pressure.
72' - SAVE! Milan counter rapidly and Kalinic gets free on the edge of the box - but his low drive is parried away by Alisson and then Manolas makes the sliding challenge to prevent Romagnoli converting the rebound!
74' - Goal. Milan double their advantage. Calabria gets in behind the defence and flicks his shot over the goalkeeper. 0-2.
78' - Kolarov hits a free-kick into the wall; his follow-up half-volley is saved comfortably by Donnarumma.
86' - Defrel's snapshot is wide of the near post.
90'+2 - Borini somehow contrives to miss from six yards after a Milan counter sees the ball find him free at the back post.
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"The team did well in the first half and didn't give AC Milan any chances, but we were missing something in our final ball and didn't have enough quality in the final third."We went missing after they scored in the second half, which is worrying and something we should think about. We often look for excuses from a physical point of view, but the team were compact and played well in the first half."
- Eusebio Di Francesco
"They scored from their first chance and that knocked the team. The match got difficult after the opening goal. We must look forward and keep on fighting right until the end."We have a very important match next week, one where we need real self-belief if we want to win."
- Federico Fazio
The Giallorossi now have six days to prepare for their next contest, as they face league leaders Napoli at the Stadio San Paolo on Saturday evening.
They then host Torino at the Olimpico the following Friday, before Shakhtar Donetsk arrive in town to conclude the Champions League last-16 tie.
Goalscorers: Cutrone (48'), Calabria (74')
Roma: Alisson; Bruno Peres, Manolas, Fazio, Kolarov; Pellegrini (Gerson), Strootman, Nainggolan (Dzeko); Cengiz (Defrel), Schick, Perotti.
AC Milan: Donnarumma; Calabria, Bonucci, Romagnoli, Rodriguez; Kessie, Biglia, Bonaventura; Suso, Cutrone, Calhanoglu
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