Alberto Gilardino and Luca Antonelli have been forced out of Italy's Euro 2012 qualifiers against Northern Ireland and Serbia with injury.
Striker Gilardino and Antonelli had been called up on Sunday but were ruled out on Monday after medical checks at Italy's Coverciano base.
Following the checks, it was decided they would not recover from calf and foot problems in time for the clash in Northern Ireland on Friday or the home fixture against the Serbs four days later.
"In the coming hours coach Cesare Prandelli will announce who will replace them in the squad," a federation statement said on Monday.
Prandelli has been operating with three upfront but even before Gilardino's injury was announced, he said he may consider playing two forwards in the coming matches given a lack of wide options.
"I don't have a lot of forwards who can play wide. I want to put the opposition under pressure and a diamond midfield could be an alternative," said Prandelli, whose side top Group C with two wins out of two.
The coach added Fiorentina midfielder Riccardo Montolivo, a member of the ill-fated World Cup team in June, had been left out of Sunday's squad because of an ankle complaint and had not been dropped, unlike Juventus' Fabio Quagliarella.