Spain's Tommy Robredo shocked world number one Novak Djokovic 7-6, 7-5 to move into the quarter-finals of the Western and Southern Open in Cincinnati.
For the 16th-seeded Robredo the victory was his first over Djokovic since their first meeting in 2005, the Serb sweeping their next six meetings.
The loss brought a temporary halt to Djokovic's bid to become the first player to win all nine ATP World Tour Masters events during his career.
It was also another setback in the Serb's buildup to the US Open later this month after falling to Frenchman Jo-Wilfried Tsonga in the third round last week in Toronto.
Meanwhile, former world number one Roger Federer avoided tasting an upset of his own as he held off Frenchman Gael Monfils 6-4, 4-6, 6-3.
A five-time winner at Cincinnati, Federer will now face Andy Murray in the quarter-finals after the Briton had to overcome a stern test against American John Isner, the former Wimbledon champion winning 6-7, 6-4, 7-6. Third-seeded Swiss Stan Wawrinka rallied past 14th seed Marin Cilic 3-6, 6-0, 6-1 to book his place in the last-eight.