For a team that has won every major international trophy, Italy's record in Bulgaria is not a proud one - two defeats and two draws with six goals conceded dating back to 1968. Most recently they emerged with a goalless draw in a 2010 World Cup qualifier four years ago.
The Italy team to face Luboslav Penev's side in the Group B match at the Vasil Levski stadium will also have a different look to the one that impressed at Euro 2012.
Balotelli is out due to eye surgery and Cassano has been dropped, so coach Cesare Prandelli, who hopes to have Roma midfielder Daniele De Rossi ready, is expected to use a 3-5-2 formation.
Prandelli has tried the formation before - notably in the early stages of Euro 2012, where his side finished runners-up to Spain, though eventually he settled on a back four.
De Rossi, who suffered an ankle injury during Roma's 3-1 win at Inter Milan last weekend, was thought to be out, but Prandelli revealed he might recover in time.
Prandelli is also expected to favour Juventus' diminutive playmaker Sebastian Giovinco over Mattia Destro in attack alongside Destro's in-form Roma team-mate Pablo Daniel Osvaldo, who has scored in his team's first two games this season.
Roma left-back Federico Balzaretti had to pull out of the squad on Tuesday after tests showed his thigh injury would keep him out of action for a month.
AC Milan striker Giampaolo Pazzini, who has a knee problem, is unlikely to feature on Friday, though he is expected to play some part in Italy's game with Malta on Tuesday.
Cagliari defender Davide Astori has also had to pull out of the squad with a similar injury, and has been replaced with AC Milan's Francesco Acerbi.
Bulgaria, who have failed to qualify for a major tournament since 2004, have lost only once in four matches since coach Penev took over after the previous qualifying campaign, including a morale-boosting 2-1 away win over the Netherlands in May.
But this week Penev suffered a blow when striker Dimitar Berbatov, Bulgaria's all-time leading scorer with 48 goals, said he would not end his self-imposed international exile despite signalling he would be open to an approach from the coach.
Penev also decided against Valeri Bojinov's inclusion in the squad, as the former Juventus and Manchester City striker joined Italian Serie B side Verona only on Friday, with the coach concerned about his lack of match practice.
Penev will probably start with three attacking players in captain Ivelin Popov, Emil Gargorov and Stanislav Manolev, but none of them is a typical forward. PSV Eindhoven's Manolev even played as a right-back in most of his Bulgaria appearances.
For the first time in the past two decades, Bulgaria will rely on home-based midfielders only, with Ludogorets' Svetoslav Dyakov, Litex Lovech's Georgi Milanov and Levski Sofia's Vladimir Gadzhev destined for a place in the starting line-up.
Bulgaria are struggling to sell tickets for the qualifier and the domestic football federation has begun handing out free tickets to the
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