Belgian Kristof Vliegen won a third-set tie break to upset eighth-seeded American James Blake 6-4, 3-6, 7-6 in the second round of the Madrid Masters on Wednesday.
Blake has won five titles this year and came into the tie having won back-to-back tournaments in Bangkok and Stockholm.
It was, however, the 24-year-old Vliegen, the straight-sets winner of the only previous encounter between the two earlier this year, who started stronger.
He broke Blake's opening service game and held firm to take the first set with some controlled tennis.
The American was clearly frustrated and struggled to find his range until he broke Vliegen midway through the second to get back into the match.
Blake looked to be in control as he raced to a 3-1 lead in the third but his opponent struck back to go 4-3 up.
Again the match swung Blake's way as he broke back but he then lost his serve again to take the set to a tie break.
Both players made errors until Vliegen served out with an ace to take the tie break 7-5 after just over two hours of play.
Earlier, in-form tenth-seeded Chilean Fernando Gonzalez, who lost in the final in Vienna last week, overcame Thailand's Paradorn Srichapan 7-5, 6-7, 6-4.
Last year's semi-finalist American Robby Ginepri knocked out 12th seed Mario Ancic of Croatia in straight sets 7-6, 7-6 and Germany's Tommy Haas eased past Dominik Hrbaty of Slovakia 6-3, 7-6.
World number two and second seed Rafael Nadal begins the defence of his title later on Wednesday, taking on qualifier Mardy Fish of the United States.
Last year's runner-up and third seed Ivan Ljubicic faces Britain's Andy Murray, ninth seed Marcos Baghdatis plays Russian Marat Safin, who won the tournament in 2004, and Spaniard Juan Carlos Ferrero plays Sweden's Robin Soderling.
