Sergio Parisse, so often the spearhead of Italy, looks set to inspire the team by his absence when they face Wales at the Stadio Olimpico on Saturday (NZT Sunday).
The captain will miss his first Six Nations rugby match in nine years without injury as an excuse after he was banned for 30 days by French Top 14 officials for swearing at a referee last weekend after being sent off.
The Italians have quietly raged against the sanction, which doesn't end until two days after the tournament.
Italy coach Jacques Brunel had prepared to play without Parisse since the weekend, but was still disappointed at the decision.
"I've seen the TV pictures and I'm convinced he didn't say anything to the official, other than to ask for a yellow card to be shown to an opponent. The official got it wrong," Brunel said. He hoped Parisse's club, Stade Francais, appeals.
"All we can do now is focus on trying to beat Wales. I've tried to change as little as possible in order for us to manage that.
"We can't get caught up with the absence of Parisse. Other players can influence the game and we cannot be over-dependent on the one player."
Tighthead prop Martin Castrogiovanni was made skipper and Manoa Vosawai picked at number eight for only his third start since his debut in 2007.
"Playing in place of my captain in front of 65,000 people gives me a huge charge," Vosawai said.
"I wish Sergio was playing, so I'm going to dedicate my performance for him."
The inclusion of Vosawai and lock Antonio Pavanello for new father Quintin Geldenhuys fills the pack with six players from Benetton Treviso.
Two more clubmates, halves Edoardo Gori and flyhalf Kristopher Burton, replaced Tobias Botes and Luciano Orquera, who were made scapegoats for the 34-10 loss to Scotland two weeks ago.
Orquera, a star of the opening-round upset of France, conceded an intercept try to the Scots in a subpar display. But the Italians also knew they weren't aggressive enough at the breakdowns at Murrayfield, and blew most of the momentum they'd earned from beating France.
Prop Andrea Lo Cicero will tie Alessandro Troncon for most Italy caps when he appears in his 101st test. Lo Cicero and flanker Alessandro Zanni were the only survivors of Italy's second and last win over Wales, in 2007.
"Sergio's absence will be felt," Zanni said, "but I'm sure if we can give more than 100 percent we can make up for it."
Wales has enjoyed having almost two weeks to get ready for Italy, as interim coach Rob Howley wasted little time sticking to the side which downed France 16-6 in Paris.
Midfielder Jamie Roberts said it was a good move by Howley, and a deserved reward for the players who ended Wales' eight-test losing streak.
"A win can not only do a lot for your confidence but it can also do a lot for the way you play the game," Roberts said.
"When you have suffered eight defeats you can play not to lose, rather than going out there to play to win.
"France was a tricky match because it was very much like that.
"Now that monkey is off our back there is more focus on our backline to express ourselves so there is definitely more to come from us. The early selection is important because it has given us clarity and extra time to prepare and everyone is comfortable together."
Italy: Andrea Masi, Giovanbattista Venditti, Tommaso Benvenuti, Gonzalo Canale, Luke McLean, Kristopher Burton, Edoardo Gori; Manoa Vosawai, Simone Favaro, Alessandro Zanni, Francesco Minto, Antonio Pavanello, Martin Castrogiovanni (captain), Leonardo Ghiraldini, Andrea Lo Cicero. Reserves: Davide Giazzon, Alberto De Marchi, Lorenzo Cittadini, Quintin Geldenhuys, Paul Derbyshire, Tobias Botes, Luciano Orquera, Gonzalo Garcia.
Wales: Leigh Halfpenny, Alex Cuthbert, Jonathan Davies, Jamie Roberts, George North, Dan Biggar, Mike Phillips; Toby Faletau, Justin Tipuric, Ryan Jones (captain), Ian Evans, Andrew Coombs, Adam Jones, Richard Hibbard, Gethin Jenkins. Reserves: Ken Owens, Paul James, Craig Mitchell, Alun-Wyn Jones, Sam Warburton, Lloyd Williams, James Hook, Scott Williams.