Rafael Nadal's hopes of lifting a ninth Barcelona Open title are over after a surprise 6-4 7-6 (8-6) defeat to Fabio Fognini on Thursday.
The world number four has been dominant at this event over the last decade, with Fernando Verdasco and Kei Nishikori the only other men to lift the title since 2005.
However, for the second successive year he has failed to reach the final, with Fognini producing a stunning display highlighted by powerful backhands and great athleticism.
There was little sign of a shock in the first set until the Italian saw a glimpse of an opening in the final game. Although he failed to convert an initial set point, he was not be denied as he moved ahead.
The often unpredictable Fognini recorded a second successive win over Nadal – having beaten him at the Rio Open in February – with the aid of a tie-break, the world number 30 holding on despite Nadal's best efforts.
Defending champion Nishikori had no such problems as he swept aside Santiago Giraldo 6-2 6-1, the top seed winning five successive games at the start of the second set to see off the Spaniard.
He will be joined in the last eight by David Ferrer after his 6-3 6-4 win over Elias Ymer, while seventh seed Roberto Bautista Agut cruised through after a tight opening set against Pablo Cuevas, the Spaniard winning 7-6 (7-5) 6-2.
Fognini will meet Pablo Andujar after he also produced a third round surprise, the Spaniard knocking fifth seed Feliciano Lopez out 6-3 6-4.
Meanwhile, Martin Klizan, Philipp Kohlschreiber and Tommy Robredo are also into the last eight after straight-set victories on Thursday.