Giorgio Chiellini was on Wednesday ruled out of Italy's World Cup qualifying deciders with Switzerland and Northern Ireland after failing to recover from a thigh injury.
The European champions' captain was among those in doubt for the key matches in qualification for the 2022 tournament in Qatar but the Italian Football Federation said he will leave the national team's training camp on Wednesday.
Chiellini's absence is a big blow heading into Friday's clash in Rome against the Swiss, who trail Group C leaders Italy on goal difference with two games remaining for both teams.
The pair are the only sides in contention for the group's sole guaranteed place at the World Cup, which will be played over November and December next year.
Italy face Northern Ireland at Windsor Park in their final match on Monday, while Switzerland host Bulgaria.
Azzurri coach Roberto Mancini has lost both Euro 2020 icon Chiellini and starting centre-forward Ciro Immobile in less than 24 hours, and is also sweating on the availability of Inter Milan midfielder dynamo Nicolo Barella.
Injured Roma midfield pair Lorenzo Pellegrini and Nicolo Zaniolo were on Monday replaced by Immobile's uncapped Lazio teammate Danilo Cataldi and Atalanta's Matteo Pessina, who has only just returned from over a month on the sidelines.
Pessina, 24, was brought on as a stoppage-time substitute in Atalanta's 2-1 win at Cagliari on Saturday, his first appearance since a calf injury picked up in a home defeat at the hands of AC Milan in early October. (AFP)

Falcons to get new coach before Olympic qualifier
Okocha bemoans Eagles’ lack of home ground
Ajayi set for Silesia Diamond League showdown
Awoniyi fired up for Coventry after reported £9m move
Pro boxers celebrate Aboderin at 60
Ikogosi Road Race returns Oct 31
WAFCON: Ajibade insists Falcons gave everything
Dolphins begin WBPL title defence with 59-46 win
Obiejesi Ratified As President of Okija Town Union, Lagos ...Thanks Members For Endorsing Him ...Urges Them To Unite And Move The Union Forward
Onuachu, Osimhen, others set for title defences as new season begins
Hrgovic confident of Itauma upset
Rangers International going, going . . . (64,035 views)
Amaju Pinnick: A cat with nine lives (55,391 views)
Second Term: Amaju Pinnick, Other NFF Heavyweights Home to Roost •How Pinnick Broke the Jinx (53,282 views)
Current issues in Nigerian sports: Matters arising (52,883 views)
Sports Development: Zenith Bank on the zenith (52,760 views)
Missing $150,000 IAAF Grant: Solomon Dalung’s Hide and Seek game (52,636 views)
Gov. Abdullahi Ganduje’s solid footprints, commitment to sports development in Kano State (52,534 views)
NFF Presidency: Pinnick, Maigari, Ogunjobi, Okoye in Battle for Supremacy (52,046 views)
Olopade, BET9A wave of revolution in NNL (51,252 views)
Commonwealth Games 2018: Shame of Muhammadu Buhari, Solomon Dalung (49,723 views)
Ibrahimovic’s Man U exit: Whose decision is it? And in whose interest? (48,207 views)
John Mikel Obi: Segun Odegbami’s Outrageous Call! (47,585 views)