Italy's struggles in Europe's prime club competition were underlined last season as Inter, totally dominant at home for four years, were swept aside by Manchester United to go out at the first knockout stage for the third season running.
Now, leading the way in Serie A again, Inter take on England's table toppers at the San Siro with former Chelsea boss Mourinho bestriding the tie.
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Holders Barcelona are in action on Tuesday where their stranglehold on German clubs and VfB Stuttgart's weakness against Spaniards points to only one eventual result.
French champions Girondins Bordeaux travel to Olympiakos Piraeus on Tuesday while Sevilla will have to dig out their thermals for their Wednesday trip to CSKA Moscow.
It is the San Siro, though, which draws the eye as two Champions League-winning managers of contrasting personalities go head-to-head.
Mourinho won the competition with Porto before going close with Chelsea, while the Londoners' latest import, Carlo Ancelotti, lifted it twice with AC Milan.
Outwardly the two men could not be more different as Mourinho delights in making waves them riding then for all he is worth, while Ancelotti seems content to go about his work in a businesslike, under-stated manner.
The two men were anything but friends as they clashed in previous Milan derbies but Mourinho knows better than anyone that Chelsea are no longer cowed by big-name reputations.
Having recovered from an end-of-year domestic wobble, they are now four points clear in the Premier League and on course to win the title for the first time since Mourinho's days.
Inter's Serie A lead has been whittled down to five points after three successive draws and while Didier Drogba is scoring for fun for Chelsea, Inter's Samuel Eto'o is struggling for form and fitness.
Inter have not beaten an English team in their last five attempts, failing to score in their last four.
Barcelona, so fortunate to get past Chelsea in the semi-finals last season, also have statistics on their side against a Stuttgart team who have lost seven and drawn three of their last 10 games against Spanish opposition while Barcelona have won 11 and drawn two of their last 13 Champions League games against German teams.
However, Stuttgart will hope their domestic run of seven wins in eight games, topped by Saturday's 5-1 win at Cologne, will prove more important.
Barcelona maintained their Spanish League lead with a 4-0 win over Racing Santander on Saturday and though they have lost only one league match all season they have not sparkled in Europe and will have to step up a level.
