Barcelona's hopes of winning the Champions League for the fourth time in eight seasons are hanging by a thread after a 2-0 defeat to AC Milan on Wednesday, while Galatasaray and Schalke played out an entertaining 1-1 draw.
The Catalans may be running away with La Liga, but they met their match in Milan in the first leg of their last-16 tie at the same venue where they suffered a fatal defeat to Inter Milan in the 2010 semi-finals.
As they usually do, Barca monopolised possession in the San Siro, but they were made to pay for their complete lack of a cutting edge as they mustered just two attempts on target all evening.
Milan, who are unbeaten in seven Serie A games in 2013, set out to frustrate their visitors but they also managed to pose a threat at the other end, and second-half goals from Ghanaian duo Kevin-Prince Boateng and Sulley Muntari proved the difference on the night.
Boateng volleyed home from the edge of the area just before the hour mark after a Riccardo Montolivo free-kick appeared to come off the arm of Cristian Zapata and into his path.
Barcelona's protests were waved away by Scottish referee Craig Thomson as Milan's 400th European Cup goal was allowed to stand, and the visitors' night took another, greater, turn for the worse nine minutes from time.
A delicious flick by Stephan El Shaarawy set up Sulley Muntari, who showed exquisite technique to volley past Victor Valdes.
"Milan were really well organised and in the first half we controlled the game but we didn't create as many chances as we'd have liked," said Barcelona assistant coach Jordi Roura, who still believes the tie can be saved.
"The result is what it is - it's a setback, but it's not a disaster."
Milan coach Massimiliano Allegri described the result as "a great win for us" and added that he "never believed we would be going to the Nou Camp with a 2-0 advantage."
The night's other game in Istanbul may not have appeared as glamorous, but there was still plenty of intrigue surrounding a Galatasaray side that had recent signings Wesley Sneijder and Didier Drogba in its ranks as they faced Schalke.
It was another Galatasaray player that grabbed the limelight, though, as the hosts took a 12th-minute lead.
A thumping finish from Burak Yilmaz for his seventh goal in seven games in this season's Champions League opened the scoring, and former Schalke player Hamit Altintop then rattled the crossbar.
However, Schalke had chances too and got a deserved equaliser on the stroke of half time at the end of a blistering counter-attack, with Jefferson Farfan setting up Jermaine Jones to thump home first-time.
"We are really happy with the result," said Jones, as Schalke, struggling domestically just now, go into the second leg with the upper hand.
"We made one or two mistakes and conceded the goal, but all together we played well."
The second legs of both ties will be played on March 12.