Italy captain Sergio Parisse has been ruled out of Saturday's RBS 6 Nations clash against Wales at the Stadio Olimpico.
In a hammer-blow for the Azzurri, number eight Parisse has not recovered from a foot injury suffered during last weekend's 29-0 home loss to France.
Italy team manager Luigi Troiani said at a press conference in Rome that Parisse had made considerable progress since suffering his injury four days ago.
"He has made great progress since Sunday, walking normally," Troiani said. "But to play him in Saturday's game might impair the normal recovery time."
Parisse will be replaced in the back row by Samuela Vunisa, who moves from openside flanker, with veteran Mauro Bergamasco handed the number seven shirt.
Leicester hooker Leonardo Ghiraldini will take over the captaincy reins from Parisse as Italy look to thwart Wales' Six Nations title bid.
Other changes made by head coach Jacques Brunel from the France clash see starts for Zebre fly-half Kelly Haimona, who has recovered from an injury that ruled him out of the France encounter, and long-serving prop Martin Castrogiovanni.
And there is also a chance in the front row for Ghiraldini's Leicester colleague Michele Rizzo, who replaces the injured Matias Aguero.
Highly-experienced forwards Quintin Geldenhuys and Robert Barbieri, meanwhile, are on the bench.
Italy will be looking to bounce back from last week's crushing defeat and Brunel underlined his disappointment with the display against France.
"We wanted to build on the victory (against Scotland) in Edinburgh, but we did not succeed," Brunel said.
"I expect a tough game on Saturday, but I expect that we will give a different picture from the one seen last Sunday.
"Wales will try to impose its own rhythm, its intensity, its power.
"They are a team that has confidence in its game, and we expect a Welsh XV that will have the ability to apply pressure with ball in hand and with the boot."
Saturday's encounter will be a third home game for Italy in this season's tournament, but they have so far scored just three points at home, going down to France and also being beaten 26-3 by Ireland.
They have, though, beaten Wales twice from seven previous Six Nations starts in Rome, even if the Azzurri - especially without Parisse - go into battle as huge underdogs.
Wales are currently third in the table on points difference behind leaders England and second-placed Ireland, and realistically they need to better their record Six Nations win in Rome - 38-8, 10 years ago - to maintain hopes of a third Six Nations title during the past four years.
Italy team: L McLean (Sale); L Sarto (Zebre), L Morisi (Treviso), A Masi (Wasps), G Venditti (Zebre); K Haimona (Zebre), E Gori (Treviso); M Rizzo (Leicester), L Ghiraldini (Leicester, capt), M Castrogiovanni (Toulon), G Biagi (Zebre), J Furno (Newcastle), F Minto (Treviso), M Bergamasco (Zebre), S Vunisa (Zebre).
Replacements: A Manici (Zebre), A De Marchi (Sale), D Chistolini (Zebre), Q Geldenhuys (Zebre), R Barbieri (Leicester), G Palazzani (Zebre), L Orquera (Zebre), E Bacchin (Treviso).