Martin Castrogiovanni has been ruled out of the rest of the World Cup because of a tumour in his sciatic nerve which requires surgery.
The veteran tighthead is one of three Italians who have left the squad ahead of their final game against Romania, however Italian medics are optimistic that Castrogiovanni's tumour is benign.
It appears he will require surgery on the problem, and was the reason for his absence during Sunday's narrow loss to Ireland.
That ended Italy's hopes of reaching the last eight, but they need to beat Romania to finish third in the group and secure qualification for the 2019 edition.
"Martin has pain on a sciatic nerve and after a check doctors found a tumour pressing on his fifth vertebra that is causing inflammation and pain,” team manager Luigi Troiani said.
“We are sure it is benign and tomorrow he will fly to Milan to see a specialist. The likelihood is he will require surgery.”
Joining Castrogiovanni on the sidelines are prop Michele Rizzo and centre Gonzalo Garcia who have both suffered knee injuries.
Earlier in the tournament centre Andrea Masi tore his Achilles tendon, while centre Enrico Morisi and wing Angelo Esposito were ruled out before Jacques Brunel’s squad had left for England.
The team also had to do without captain and talisman Sergio Parisse for their first two matches as he was recovering from surgery to reduce a haematoma on his left calf.
There was better news for vice-captain Leonardo Ghiraldini, who missed the 16-9 defeat by Ireland at the Olympic stadium on Sunday with a thigh injury.
He has continued his work with the squad’s medical staff and the hope is he will be back for the Romania match, which Italy must win to secure third place and a spot at the 2019 World Cup.
“Leo is better and confident he can play on Sunday,” Troiani said. “He will have some checks over the next couple of days to make sure.”
Italy have called up two front row forwards to prepare for the clash against Romania, with Alberto de Marchi and Andrea Lovotti set to join the squad.