Prandelli has built his Italy team around Cassano since taking over from Marcello Lippi following the 2010 FIFA World Cup South Africa™. Cassano has been ever-present for Italy under Prandelli, who repeatedly spoke of his faith in the often errant star.
But the 28-year-old Sampdoria forward has not been called up for the friendly because he has not played for his club this month after falling out with their president Riccardo Garrone. Cassano is alleged to have seriously insulted Garrone in an argument at the club's training centre and Sampdoria have asked football authorities for permission to terminate his contract.
It is not the first time Cassano has found himself in hot water, he has a history of falling out with team-mates, coaches and even authorities. And Prandelli says he is going to have to change his ways.
"I'm not condemning him. He's made my work difficult but when he returns to playing, with Samp or elsewhere, I'll be ready to recall him," said Prandelli. "It seemed as if all (Cassano's) problems were resolved, I don't know what happened. As I've said before, he's one of those youngsters who needs help.
"But out of the maximum respect for Sampdoria and their president we didn't want to create any issues so I decided not to call him up. Cassano realised straight away that he's created a problem for the national team, I can't give continuity to my attacking plans but I hope we'll be able to see the project again in the spring.
"From my side I'll recall him when he's changed his behaviour. I'm not disappointed, it's something that can happen, I don't know the details but I respect Garrone."
While Cassano is out, Prandelli does have Manchester City forward Mario Balotelli back from injury. "Balotelli's doing well in England and I also expect him to do good things in blue (Italy's colours)," said Prandelli.
"I hope Mario can repeat with us the incredible performance he's shown in the Premier League. He's been smiley and he's shown the desire to play, we all hope that this is going to be the start of great things in his career."
He's not the only player coming back as Romania can call upon their former captain Adrian Mutu again following a ban for using a banned substance. The friendly acts as a rare break from UEFA EURO 2012 qualifying.
Italy are in good shape in Group C, leading it by three points from Slovenia after four games. Romania, however, have started badly in Group D and are well off the pace after no wins in three matches.
Meanwhile Italian president Giancarlo Abete defended the selection of Argentine-born midfielder Cristian Ledesma of Lazio. He's the second foreign born player after Juventus striker Amauri - a Brazilian by birth - to have been called up since Prandelli took over in July.
"The coach is free to pick all the players who hold an Italian playing licence," said Abete. "Ledesma is one of those, he's an Italian citizen in every respect, just as is Amauri. On top of that, he's having a great season with Lazio and the friendly against Romania will allow the coach to experiment before March (when the qualifiers resume)."