Now at Galatasaray, the three-time Serie A winner stands on the brink of potentially the biggest continental clash of his career: a do-or-die home meeting with Juventus on Wednesday night.
Despite taking over a team fresh from a 6-1 home drubbing to Real Madrid back in September, the Italian and his side can make it out of a group few would have expected them to survive when the draw was made.
Unfortunately, history is very much against him. In 2003-04, Mancini made his debut in Europe's top competition with Lazio and failed to make any sort of positive impact. The Rome outfit was arguably the favorite for a group containing Chelsea, Besiktas and Sparta Prague but finished bottom, with the team's only win coming, coincidentally, in Istanbul.
A year later, he was in his first season of his four-year spell at Inter and he fared better. After topping a group with an unbeaten record, Inter knocked out Porto in the round of 16, but crashed out to city rival AC Milan in the following round, losing both legs as the Rossoneri went on to make the final.
ROBERTO MANCINI | ALL-TIME CHAMPIONS LEAGUE STATS
Porto once again fell victim to the Nerazzurri the following year as Mancini's men negotiated a straightforward group and overcame Ajax in the last 16, but suffered a shock quarterfinal defeat to competition débutante Villarreal.
That was the last time the 49-year-old led a team to the last eight. In both 2006-07 and his final term at San Siro, the club was knocked out in the second round, first losing to Valencia before then being eliminated by Liverpool.
The loss to Rafa Benitez's side was particularly controversial. Luis Figo refused to come off the bench in the second leg at San Siro, underlining that Mancini had totally lost the support of the dressing room. The former Sampdoria star handed in his resignation and, though he reversed his decision, he was ultimately forced out at the end of the season.
Inter had domestic dominance that any team would dream of - winning three Calciopoli-conditioned Scudetti (one of them controversially assigned in the courts, which has since been discredited) but failed to establish itself in Europe under Mancini. Inter was European champion within two years under Jose Mourinho - despite the sale of Zlatan Ibrahimovic the previous summer.
At Manchester City, despite lifting the 2012 Premier League title, he hit his continental nadir. With enough money to mold the team completely in his own image, he failed to make it past two admittedly tough groups (Bayern, Napoli and Villarreal in 2011-12, and Real Madrid, Borussia Dortmund and Ajax in 2012-13). In the second term, the Etihad outfit finished bottom of its pool, having failed to win a single game.
And so Tuesday's match with Juventus is a crossroads for Mancini. Few expected anything from Galatasaray when the group was drawn, yet if the club can see off Juventus it will be in the last 16 for the second year running.
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