A week after leaders Juventus suffered a shock 2-1 reverse at Fiorentina to allow Roma to close to within one point, the Turin giants have reason to be looking over their shoulders as they chase a record sixth consecutive crown.
Roma are only one point behind in second before hosting Cagliari, three days after sweeping Sampdoria aside 4-0 in the Italian Cup, and well-oiled Napoli are only three points further behind.
In October last year Lorenzo Insigne hit a second-half brace as Napoli's fast-paced flowing game stunned the Rossoneri on their way to a chastening 4-0 win while Milan were under the helm of Sinisa Mihajlovic.
More than a year on, Milan coach Vincenzo Montella has fans believing that, with some luck, they could pip Roma and Napoli to a third place finish and a possible return to Europe's premier club competition.
Milan set out their stall last October with a deserved 1-0 win over Juventus, their first of two over the champions so far this season ahead of the sides' Italian Cup quarter-final next Wednesday.
Napoli midfielder Jorginho told Radio Kiss Kiss: "It won't be an easy game. They are an organised side that always plays a little bit better at home."
Milan owner and president Silvio Berlusconi is set to hand the club reins to new Chinese owners following completion of an ongoing takeover this March, and Montella is so far succeeding where Cristian Brocchi, Mihajlovic, Filippo Inzaghi and Clarence Seedorf failed -- at least in terms of keeping fans' hopes of qualifying for Europe alive after Christmas.
But a big test comes Saturday. Milan haven't beaten Napoli since 2014 and will be without key defender Alessandro Romagnoli and Manuel Locatelli, whose one-match suspensions deprive Milan of stability at the back and a hard-working midfielder adept at creating chances out of nothing up front.
They are set to be replaced respectively by Gustavo Gomez and Argentine midfielder Jose Sosa.
Insigne (5), Dries Mertens (12), Jose Callejon (7) and Marek Hamsik (6) share 30 of Napoli's league-leading tally of 45 goals so far this season, and key striker Arkaduisz Milik (4) has yet to return from a cruciate knee ligament injury suffered in October.
Colombian Carlos Bacca, who spent a brief spell on the injury sidelines, is Milan's top scorer with eight goals, just ahead of Suso (5) and Gianluca Lapadula (4).
But the Rossoneri have lost only once, to Udinese, at the San Siro this season and goalkeeper Gianluigi Donnarumma said: "Playing Napoli is always an emotional affair, and we want to do well for the fans.
"It's a crucial game for us because we have to make up for the points we've dropped recently."
A third-place finish guarantees a play-off to join the group stages of the Champions League and Lazio striker Sergej Milinkovic-Savic, who has hit three goals in his last seven games including the opener in a 2-1 win over Atalanta last week, said: "We want the Champions League, but we're not the only ones with this objective."
Juventus, who host Lazio on Sunday, will be expected to bounce back from last week's reverse. Lazio lost 1-0 to the champions in Rome earlier this season and have already suffered defeat to AC Milan, Roma and Inter this campaign.
Fixtures (times GMT)
Chievo v Fiorentina (1700), AC Milan v Napoli (1945)
Juventus v Lazio (1130 GMT), Bologna v Torino, Empoli v Udinese, Genoa v Crotone, Palermo v Inter Milan, Pescara v Sassuolo (all 1400), Atalanta v Sampdoria (1700), Roma v Cagliari (1945)