Stephan El Shaarawy, Ciro Immobile and Federico Bernardeschi lead Italy out against Lithuania, while Rafael Toloi gets his Azzurri debut.
The World Cup qualifier kicks off in Vilnius at 19.45 UK time (18.45 GMT).
For Lithuania vs. Italy tips and a full betting preview, visit Eurotips.
The Azzurri won both group games so far by 2-0 scorelines, against Northern Ireland and Bulgaria last week.
Roberto Mancini rotates the squad again, having lost Marco Verratti and Alessandro Florenzi to injury as well over the last few days.
Manuel Locatelli therefore starts for the second time in three games, and he is joined by Lorenzo Pellegrini and the first start for Atalanta midfielder Matteo Pessina.
Immobile returns upfront, flanked by Bernardeschi and El Shaarawy, rather than Federico Chiesa.
Atalanta’s Brazil-born defender Toloi is given his debut and thrown in from the start, with Inter’s Alessandro Bastoni, Roma’s Gianluca Mancini and Emerson Palmieri of Chelsea.
Lithuania only played one match in the group so far, a narrow 1-0 defeat away to Switzerland on Saturday.
Their approach is very much defend and counter, with lone striker Fedor Chernych upfront, so Italy will require some patience.
Lithuania: Svedkauskas; Mikoliunas, Beneta, Girdvainis, Vaitkunas; Dapkus, Simkus, Slivka; Novikovas, Sirgedas; Cernych
Lithuania bench: Adamonis, Driomovas, Gaspuitis, T Eliosius, Laukzemis, Silkaitis, Petravicius, Lasickas, Romanovskji, Valskis, D Kazlauskas, Baravykas
Italy: G Donnarumma; Toloi, Bastoni, Mancini, Emerson; Pellegrini, Locatelli, Pessina; El Shaarawy, Immobile, Bernardeschi
Italy bench: Sirigu, Meret, Di Lorenzo, Spinazzola, Belotti, Insigne, Lazzari, Sensi, Chiesa, Acerbi, Barella, Bonucci
Ref: Raczkowski (POL)