Antonio Cassano returns with Diego Milito as Inter welcome second-placed Napoli with Edinson Cavani, Marek Hamsik and Lorenzo Insigne.
This is potentially a decisive clash to see who will be the main challengers for leaders Juventus and kicks off at San Siro at 19.45 GMT.
Wesley Sneijder is again left out amid a contract dispute, while Walter Samuel sits out a ban.
Andrea Stramaccioni is also missing the injured Jonathan, Ricky Alvarez, Gaby Mudingayi, Joel Obi, Dejan Stankovic and Cristian Chivu.
Cassano returns after his two-match ban for insulting the referee, joining Milito in attack, but Rodrigo Palacio is only on the bench.
Esteban Cambiasso steps into centre-back for the suspended Samuel, chosen ahead of Matias Silvestre.
Napoli have a full squad to choose from, as Hamsik is able to start despite suffering from flu symptoms.
Goran Pandev is only fit for the bench against his former club, so Insigne partners on-form hitman Cavani.
There are reports that former Napoli star Ezequiel ‘Pocho’ Lavezzi will be in the stands tonight along with President Aurelio De Laurentiis.
There has been snow in Milan over the last few days and the temperature is -4 degrees Celsius.
Inter: 1 Handanovic; 23 Ranocchia, 19 Cambiasso, 40 Juan Jesus; 55 Nagatomo, 4 Zanetti, 21 Gargano, 14 Guarin, 31 Pereira; 99 Cassano, 22 Milito
Inter bench: 12 Castellazzi, 27 Belec, 6 Silvestre, 7 Coutinho, 8 Palacio, 17 Mariga, 24 Benassi, 28 Pasa, 33 Mbaye, 41 Duncan, 52 Romanò, 88 Livaja
Napoli: 1 De Sanctis; 55 Gamberini, 28 Cannavaro, 5 Britos; 11 Maggio, 85 Behrami, 88 Inler, 18 Zuniga; 17 Hamsik; 24 Insigne, 7 Cavani
Napoli bench: 22 Rosati, 2 Grava, 4 Donadel, 6 Aronica, 8 Dossena, 9 Vargas, 14 Campagnaro, 15 Colombo, 16 Mesto, 19 Pandev, 20 Dzemaili, 21 Fernandez