Werder Bremen produced a rousing fightback at the San Siro to eliminate favourites AC Milan from the UEFA Cup on Thursday and heap further pressure on coach Carlo Ancelotti.
The Italian shrugged off fresh speculation this week that he could be sacked in May but will face further calls for his head after Claudio Pizarro scored twice as Werder hit back from 2-0 down to draw 2-2 and reach the last 16 on away goals after the tie ended 3-3 on aggregate.
Holders Zenit St Petersburg eased through, while former winners Galatasaray, CSKA Moscow and Ajax Amsterdam all qualified for the second knockout round. Valencia, who won the trophy in 2004, bowed out to Dynamo Kiev.
Milan have been crowned European champions seven times but the UEFA Cup remains the only major European trophy they have yet to win.
Trailing Serie A leaders Inter Milan by 11 points and with their title hopes fading fast, Ancelotti and Milan appeared on course to at least make UEFA Cup progress when first-half goals from Andrea Pirlo and Alexandre Pato put the Italians 3-1 up in the tie.
But Peruvian striker Pizarro nodded in a Diego free kick on 68 minutes and 10 minutes later he tucked away a cross to send the Bundesliga side through to a last 16 clash with St Etienne.
Zenit ousted VfB Stuttgart 4-2 on aggregate while tension was in plentiful supply at the Ali Sami Yen stadium where Galatasaray scored a last-minute winner to knock out Girondins Bordeaux in a seven-goal thriller, staying on course for the final in their home city of Istanbul on May 20 which will be staged at the home of their arch-rivals Fenerbahce.
Turkey defender Sabri Sarioglu struck from the edge of the penalty area to give the 2000 UEFA Cup winners a 4-3 first knockout round victory.
Bordeaux had threatened to spoil coach Bulent Korkmaz's first game in charge of last season's Turkish champions by taking a first-minute lead, the opening goal of the tie.
Bulent, a former Turkish international and Gala captain who was appointed on Monday after Michael Skibbe was sacked, had barely taken his seat before David Bellion ran on to Diego Placente's long ball and fired home.
The hosts then took control with two quick goals just before halftime from Arda Turan and substitute Harry Kewell followed by another midway through the second half from midfielder Arda.
Bordeaux stormed back to level at 3-3 through Marouane Chamakh and Fernando Cavenaghi with 15 minutes remaining and were heading through on away goals until Sabri's winner.
"We needed a victory like this," Galatasaray chairman Adnan Polat told reporters. "We experienced a short crisis period. We saw in this match signs that we will recover quickly."
Galatasaray next face Hamburg SV who progressed 4-0 on aggregate against NEC Nijmegen.
CSKA Moscow, the 2005 winners, took full advantage of an under-strength Aston Villa team with a 3-1 aggregate win.
Villa manager Martin O'Neill had made no secret that his season's goal was securing a Champions League qualification place in the Premier League and fielded just three of the starting side that lost 1-0 to Chelsea last weekend.
The competition's leading scorer Vagner Love took his tally to 10 with a crisp finish in stoppage time to complete a 2-0 win in sub-zero temperatures in the Russian capital.
CSKA now play Ukraine's Shakhtar Donetsk who drew 1-1 at White Hart Lane to put out twice winners Tottenham Hotspur 3-1 over the two legs. Spurs, who take on Manchester United in the League Cup final on Sunday, fielded an under-strength side.
Dynamo Kiev knocked out Valencia on away goals after a 2-2 draw in Spain, setting up a clash with Metalist Kharkiv which will be the first meeting between two Ukraine sides in European club competition.