Goran Pandev leads Napoli against his former teammates, as Inter start Giampaolo Pazzini and Douglas Maicon.
Claudio Ranieri hopes to continue his amazing start on the Nerazzurri bench, having won both his games since replacing Gian Piero Gasperini.
He has to do without Wesley Sneijder, Ivan Cordoba, Thiago Motta, Andrea Poli, Emiliano Viviano and the suspended Andrea Ranocchia for tonight's clash.
Pazzini was initially ruled out when he sprained his ankle against CSKA Moscow, but has recovered to start in attack.
Diego Forlan is ineligible for the Champions League, so is well rested. Diego Milito had a muscular problem in training on Friday and is not even on the bench.
The real shock is that Maicon is given his first start of the campaign. He underwent knee surgery over the summer and hasn't played for Inter since the 1-1 against Napoli on May 15.
Napoli made the trip to San Siro without hitman Edinson Cavani, who sprained his ankle in the 2-0 victory over Villarreal on Tuesday.
He is replaced in the trident attack by Pandev, who is on loan from Inter, joining Lavezzi and Hamsik.
The Partenopei are also missing the injured Blerim Dzemaili and Miguel Angel Britos, but Salvatore Aronica shook off a knock to start.
Coach Walter Mazzarri will be particularly eager to get a good result at San Siro, as today is his 50th birthday.
Inter: Julio Cesar; Maicon, Lucio, Samuel, Chivu; Zanetti, Cambiasso, Obi; Alvarez; Forlan, Pazzini
Inter bench: Castellazzi, Nagatomo, Stankovic, Coutinho, Castaignos, Muntari, Zarate
Napoli: De Sanctis; Campagnaro, Cannavaro, Aronica; Maggio, Inler, Gargano, Zuniga; Hamsik, Pandev; Lavezzi
Napoli bench: Rosati, Fideleff, Dossena, Mascara, Santana, Fernandez, Chavez
Think you know your Italian football? Share your knowledge, tips and comments to win cash prizes in OLBG's World Cup tipster competition  - £10,000 to be won!