Roberto Bautista Agut crashed out to Arthur Rinderknech in the second round of the Swiss Open Gstaad on Wednesday, while fifth seed Federico Delbonis also failed to progress.
Rinderknech, who is ranked exactly 100th in the world, picked up the biggest win of his career in style as he dispatched of second seed Agut with a comfortable 6-2 6-4 victory
In another upset, world number 155 Hugo Gaston laid down an early marker with a first-set demolition of Delbonis, who lost out to eventual winner Pablo Carreno Busta in the Hamburg European Open semi-finals last week, before he triumphed in three sets, 6-0 6-7 (2-7) 7-6 (7-3).
Fourth seed Cristian Garin cruised past Marc Polmans 6-3 6-0 to wrap the match up in less than an hour and seal his fifth ATP quarter-final of 2021.
Another semi-finalist in Hamburg, Laslo Djere survived a second-set scare to eliminate Zizou Bergs with a 6-2 4-6 6-2 win, which sets up a last-eight tie with Rinderknech.
At the Croatia Open in Umag, fourth seed Richard Gasquet battled past qualifier Alessandro Giannessi to secure a 7-6 (7-4) 6-4 victory.
Top seed Albert Ramos-Vinolas also progressed, winning 7-5 6-4 to eliminate Duje Ajdukovic on his home turf.