Inter have Wesley Sneijder and Diego Forlan against Roma, who use Rodrigo Taddei and Simone Perrotta as full-backs in tonight's San Siro battle.
Both clubs are in crisis after a series of defeats in Serie A and Europe with Coaches Gian Piero Gasperini and Luis Enrique already looking at lists of potential replacements.
The Nerazzurri have lost all three of their official games under Gasperini, but he moves to the 3-5-2 system with Sneijder in a deep midfield role.
The injury list includes Dejan Stankovic, Thiago Motta, Andrea Poli, Emiliano Viviano, Ivan Cordoba, Cristian Chivu and Douglas Maicon.
Roma have problems too, as they went out of the Europa League in the play-offs and lost 2-1 at home to Cagliari.
Cicinho and Juan are injured with Jose Angel suspended, so Simon Kjaer makes his debut in the Giallorossi jersey. Bizarrely, winger Taddei and midfielder Perrotta are rediscovered as full-backs in the 4-3-3 system.
The trident attack is changed, as Bojan Krkic is dropped in favour of Under-21 Italian international and ex-Chelsea striker Borini.
There were reports Pablo Daniel Osvaldo would also be dropped, but he retains his spot with Totti.
The game could be affected by the climate, as it is raining and very windy in Milan this evening.
Inter: 1 Julio Cesar; 6 Lucio, 25 Samuel, 23 Ranocchia; 55 Nagatomo, 4 Zanetti, 19 Cambiasso, 10 Sneijder, 20 Obi; 9 Forlan, 22 Milito
Inter bench: 12 Castellazzi, 42 Jonathan, 44 Bianchetti, 77 Muntari, 7 Pazzini, 28 Zarate, 30 Castaignos
Roma: 24 Stekelenburg; 11 Taddei, 44 Kjaer, 29 Burdisso, 20 Perrotta; 16 De Rossi, 7 Pizarro, 15 Pjanic; 31 Borini, 10 Totti, 9 Osvaldo
Roma bench: 1 Lobont, 5 Heinze, 14 Bojan, 19 Gago, 22 Borriello, 77 Cassetti, 87 Rosi
See the latest Serie A predictions and betting tips with Eurotips.co.uk