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)

Aina doubtful for Villa’s Europa League clash
Oyebanji labels Oyebode football tourney talent pipeline
Adeshina bags Texas Tech student-athlete award
Portable challenges Davido, Zlatan after Carter Efe defeat
Inter plot €8m Akinsanmiro buy back after Pisa sale
Joshua’s former trainer predicts KO against Fury
Ikoyi Club set to host inter-school swimming league
Portable blames huge gambles for Carter Efe defeat
Organisers set N10m prize, Liverpool tour for Lagos tourney
Hearn labels Joshua’s boxing return ultimate comeback
3SC’s Adegoke shines as Chelle scouts NPFL players
Nigeria face Netherlands, Jamaica in 4x400m heat
Rangers International going, going . . . (63,756 views)
Amaju Pinnick: A cat with nine lives (55,077 views)
Second Term: Amaju Pinnick, Other NFF Heavyweights Home to Roost •How Pinnick Broke the Jinx (53,013 views)
Current issues in Nigerian sports: Matters arising (52,600 views)
Sports Development: Zenith Bank on the zenith (52,526 views)
Missing $150,000 IAAF Grant: Solomon Dalung’s Hide and Seek game (52,422 views)
Gov. Abdullahi Ganduje’s solid footprints, commitment to sports development in Kano State (52,272 views)
NFF Presidency: Pinnick, Maigari, Ogunjobi, Okoye in Battle for Supremacy (51,819 views)
Olopade, BET9A wave of revolution in NNL (51,011 views)
Commonwealth Games 2018: Shame of Muhammadu Buhari, Solomon Dalung (49,511 views)
Ibrahimovic’s Man U exit: Whose decision is it? And in whose interest? (47,930 views)
John Mikel Obi: Segun Odegbami’s Outrageous Call! (47,388 views)