Manchester City's Champions League hopes hang by a thread after a brace from Edinson Cavani handed Roberto Mancini's men a 2-1 defeat at Napoli.
City now need to beat German giants Bayern Munich in their final game in Group A to stand a chance of going through to the knockout stages and also require whipping-boys Villarreal to beat Napoli.
Manchester United were held 2-2 at Old Trafford by Benfica, who consequently top Group C, and now have to avoid defeat in Basel next month to secure qualification.
United were without Wayne Rooney on account of injury and they lacked his drive, as Benfica overwhelmed them early on. The Portuguese side pressed forward and were gifted an opening goal on three minutes, as Phil Jones stuck out a leg to clear a cross and shinned it into his own net. It could have been far worse as Bruno Cesar and Javi Garcia went close to adding to the lead.
Rooney's absence handed Dimitar Berbatov a rare start and he took full advantage by planting a superb header into the corner on the half hour to draw United level.
It looked like United had weathered the storm as they started the second half like they had been given a rocket by Sir Alex Ferguson and Darren Fletcher fired United ahead on 59 minutes. The lead lasted just one minute, as a poor kick from David De Gea put United in trouble and Pablo Aimar was on hand to turn the ball home after Rio Ferdinand unluckily failed to make the clearance.
Basel, who United face in a showdown for second place in Group C on December 7, beat Otelul Galati 3-2 at the Stadionul National thanks to some ruthless finishing from Fabian Frei, Alexander Frei and Marco Streller.
Manchester City were undone by Cavani, a player they have been heavily linked with in recent weeks. Mancini played down the prospect of signing the striker in the build-up to the game but the City boss may well be reassessing that statement after the Uruguayan sunk his side in Naples.
City arrived in Italy knowing a win would take them into the knockout stages, but roared on by their vociferous fans Napoli started like a train and Marek Hamsik passed up a great headed chance inside ten minutes.
Joe Hart produced a brilliant save to tip over Gokhan Inler's stinging drive. But from the resulting corner, City fell behind. Cavani stole in at the near post to flick on a header and with City declining to put a man on the near post, the ball squeezed between Hart and the woodwork.
With City riding high in the Premier League, they believe they belong among Europe's elite and their workrate earned them a leveller - with Mario Balotelli on hand to stab the ball home after the ball was parried into his path by Morgan De Sanctis.
Cavani's opener had a touch of fortune about it, but there was nothing fortunate about the second - with the forward showing superb technique to make crisp contact with a low volley that proved much too hot for Hart to handle.
How the scoreline finished 2-1 is not clear, as Napoli missed a string of chances - Hamsik hit a post and Christian Maggio failed to ram home an opening - while at the other end Balotelli was denied by De Sanctis and Samir Nasri fired over from six yards.
Bayern Munich secured themselves a berth in the knockout stages and first place in Group A with a 3-1 win over Villarreal, who bid to farewell to Europe as they are guaranteed to now finish in bottom spot.
Franck Ribery and Mario Gomez netted in the opening 23 minutes to give Bayern a flying start and Ribery then wrapped up the scoring with his second after Villarreal had pulled a goal back through Jonathan De Guzman.
Real Madrid wrapped up top spot in Champions League Group D in emphatic fashion by thrashing Dinamo Zagreb 6-2.
The Spanish giants stormed into a 3-0 lead over Dinamo Zagreb inside nine minutes with goals from Karim Benzema, Jose Callejon and Gonzalo Higuain, and Mesut Ozil made it four before 20 minutes were up.
Callejon and Benzema struck again after the interval and Madrid could have had even more goals, while late strikes from Dinamo's Fatos Beqiraj and Ivan Tomecak gave a merely cosmetic effect to the scoreline.
Ajax all but booked their place in the last 16 of the Champions League after a battling goalless draw on the road at Lyon. The 0-0 result means the sides remain separated by three points heading into the final round of fixtures, with second-placed Ajax needing to avoid defeat at home to Group D winners Real to be sure of progressing.
Lille re-ignited their hopes of progressing after claiming a deserved 2-0 victory over CSKA Moscow. Lille had only picked up two points from their opening four games but they recorded their first win in Group B thanks to second-half goals via CSKA defender Vasili Berezutsky, who put into his own net, and Moussa Sow.
Inter Milan reached the knockout stages and guaranteed top spot in Group B after Ricardo Alvarez's first-half goal helped them to a 1-1 draw at Trabzonspor. Inter started the night with their progress already guaranteed after group rivals Lille beat CSKA Moscow in an earlier kick-off, but the point in Turkey was enough to ensure they cannot be caught in top spot.