It’s Robinho, Kevin-Prince Boateng and Giampaolo Pazzini against Edinson Cavani, Marek Hamsik and Goran Pandev in a showdown for second place, dropping Stephan El Shaarawy.
This San Siro battle kicks off at 19.45 UK time (18.45 GMT). Click here for a match preview.
Napoli have a four-point advantage in the race for second, which is worth automatic qualification for the Champions League without the need for a preliminary round.
Walter Mazzarri has a full squad to choose from, so focuses on the Three Tenors Cavani, Hamsik and Pandev.
Milan must do without star striker Mario Balotelli, who begins a three-match ban for insulting the officials.
Bojan Krkic also pulled out of the squad this morning with a calf problem, joining Massimo Ambrosini and Nigel De Jong on the treatment table.
El Shaarawy had been widely expected to partner Pazzini – who returns from a micro-fracture to his fibula – and Boateng.
However, in a shock move, Coach Massimiliano Allegri has benched the Little Pharaoh in favour of the Brazilian. It’s not yet clear whether this is a tactical choice or dictated by an injury.
Napoli’s last victory in this fixture was in April 1986, followed by 10 defeats and nine draws between Serie A and the Coppa Italia.
There were reports of trouble outside San Siro ahead of the game, including the use of tear gas by police, but there are over 71,000 fans at the stadium tonight.
Milan: Abbiati; Abate, Zapata, Mexes, Constant; Flamini, Montolivo, Muntari; Boateng, Pazzini, Robinho
Milan bench: Amelia, Gabriel, Bonera, Salamon, Yepes, Zaccardo, Antonini, De Sciglio, Nocerino, El Shaarawy, Niang
Napoli: De Sanctis; Campagnaro, Cannavaro, Britos; Maggio, Behrami, Dzemaili, Hamsik, Zuniga; Pandev, Cavani
Napoli bench: Rosati, Colombo, Grava, Gamberini, Rolando, Mesto, Inler, Donadel, Armero, El Kaddouri, Calaiò, Insigne
Think you know your Italian football? Share your knowledge, tips and comments to win cash prizes in OLBG's tipster competition - £11,000 to be won monthly!