Fernando Llorente grabbed a brace as Athletic Bilbao proved their Europa League conquest of Manchester United was no fluke with a 4-2 win at Schalke in Thursday's quarter-final first leg.
Llorente struck in the 20th and 73rd minutes in Gelsenkirchen after veteran compatriot Raul had scored twice to give the German side a 2-1 lead on the hour mark before Bilbao hit three goals in the last 17 minutes.
After Llorente had levelled for 2-2, Oscar de Marcos and Iker Muniain scored in the closing 10 minutes while Schalke's Dutch striker Klaas-Jan Huntelaar hit the post with a smart volley.
Bilbao will start as comfortable favourites to make the semi-finals when the second leg is played at home next week although they will have defensive midfielder Ander Iturraspe suspended.
Raul's goals, his second a fine volley, also extended his record as Europe's deadliest striker with the 34-year-old now having 76 goals in European competition, six more than Filippo Inzaghi.
Atletico Madrid, the 2010 champions, needed a goal a minute from time to edge another German side Hanover 2-1 in Spain.
Falcao fired Atletico in front after nine minutes with Mame Biram Diouf levelling for Hanover seven minutes from half-time.
But substitute Eduardio Salvio popped up in the 89th minute to give Atletico a narrow lead.
Australian international Brett Holman and Maarten Martens scored Dutch league leaders AZ Alkmaar's goals in a 2-1 victory over Valencia, the third Spanish side in the quarter-finals.
Holman volleyed in a Martens' corner on the stroke of half-time but Mehmet Topal headed the equaliser soon after the interval.
Martens found the target from Holman's cross in the 79th-minute to give his side the upper hand ahead of the second leg.
Sporting Lisbon, who put out Manchester City in the last 16, saw off Metalist Kharkov 2-1, but were left to regret conceding a last-minute penalty against the Ukrainians.
Metalist secured their vital away goal after Sporting goalkeeper Rui Patricio had brought down substitute Marko Devic allowing Cleiton Xavier to score from the spot.
Unbeaten in their last 10 European home games, Sporting went ahead through Marat Izmailov in the 51st minute with Emiliano Insua adding a second 13 minutes later.