Serse Cosmi's debut for Palermo introduces a 3-5-2 system with Javier Pastore as a striker, while Lazio adopt a very attacking formation led by Mauro Zarate.
The new Coach took over this week after a 7-0 home defeat at the hands of Udinese proved the final straw for Delio Rossi.
Cosmi – a lifelong Roma fan – makes his first appearance on the Rosanero bench at the Stadio Olimpico at 19.45 UK time.
He has to do without Fabrizio Miccoli, Dorin Goian, Mauricio Pinilla and banned duo Arman Bacinovic and Matteo Darmian.
Palermo switch from the 4-3-1-2 system to a 3-5-2 with Pastore pushed up alongside Abel Hernandez, moving Josip Ilicic to a deeper midfield role.
Lazio need a victory to take back fourth place from Udinese, so go for broke with a very attacking formation.
Hernanes and Giuseppe Sculli join Zarate in supporting centre-forward Sergio Floccari, so Libor Kozak is left on the bench.
Cristian Ledesma and Francelino Matuzalem provide even more creativity in midfield, while goalkeeper Nando Muslera returns after spraining his ankle in the warm-up against Bari.
Coach Edy Reja had to do without Andre Dias, Mobido Diakitè, Stefano Mauri, Cristian Brocchi and Tommaso Rocchi.
Lazio: 86 Muslera; 5 Scaloni, 13 Stendardo, 20 Biava, 26 Radu; 24 Ledesma, 11 Matuzalem; 77 Sculli, 8 Hernanes, 10 Zarate; 22 Floccari
Lazio bench: 12 Berni, 2 Lichtsteiner, 16 Garrido, 81 Del Nero, 23 Bresciano, 15 Gonzalez, 18 Kozak
Palermo: 46 Sirigu; 6 Munoz, 5 Bovo, 66 Andelkovic; 16 Cassani, 23 Nocerino, 8 Migliaccio, 72 Ilicic, 42 Balzaretti; 9 Hernandez, 27 Pastore
Palermo bench: 99 Benussi, 29 Garcia, 94 Acquah, 4 Kasami, 11 Liverani, 77 Kurtic, 22 Paolucci
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!