Barcelona - Rafael Nadal's stuttering season has continued as he was stunned 6-4, 7-6 (8/6) by Italy's Fabio Fognini at the Barcelona Open on Thursday.
Nadal, an eight-time champion in Barcelona, had won four of the previous five meetings between the two, but also lost to Fognini on clay earlier this season in Rio de Janeiro.
However, despite saving three match points in the second set tie-break, a forehand error gifted Fognini a shock place in the quarter-finals where he will meet Pablo Andujar.
Defeat means Nadal has just one win against a top-10 ranked opponent in seven tournaments so far in 2015.
"To win against the best player in history on this surface means double. I gives me a huge mental boost," said Fognini, who was cheered on by WTA star girlfriend Flavia Pennetta.
"I had the chance to beat him in Rio in a very tough game in 35 degree heat when the two of us were dead by the end.
"Today, I knew I would have a chance. I tried to stick to my tactics, give my best and in the end I achieved it."
Fognini edged a tight first set with the only break of serve in the 10th game.
Nadal, though, appeared set to take the match to a deciding set when broke to lead 4-2 and 5-4 in the second.
The 14-time Grand Slam champion failed to serve it out and despite Fognini suffering a nasty fall, Nadal quickly fell behind in the tie-break.
Some sensational tennis allowed him to save three match points from 3-6 down, but a big serve from Fognini followed by Nadal's 30th error of the match sealed his fate.
Defending champion Kei Nishikori thrashed Colombian 15th seed Santiago Giraldo 6-2, 6-1 to move into the quarter-finals in a repeat of last year's final.
The Japanese top seed is making his first appearance of the season on clay in the Catalan capital, but showed no signs of rustiness early on as he romped into a 4-0 lead.
Giraldo responded by getting a break of serve back at 4-2, but Nishikori then reeled off the next seven games to take him to the brink of victory and he served it out to make the last eight with ease.
"It was a harder match than the scoreline indicates. I just played better on the decisive points," said Nishikori.
The world number five will face Roberto Bautista Agut on Friday after the Spaniard overcame Pablo Cuevas 7-6 (7/5), 6-2.
"It will be a tough match because Roberto is a good player, especially on clay. I expect there will be a lot of long points like today," he added.
Third seed David Ferrer had a slightly tougher afternoon against 19-year-old Swede Elias Ymer despite winning 6-3, 6-4.
Ferrer took the first set comfortably, but was 4-0 down in the second before winning six straight game to claim his place in the quarters.
"It was the first time I had played against him and he is a player with a great future," said Ferrer.
"I knew I wasn't playing at 100 percent and I had to keep running and stay strong mentality."
Collated results on the fourth day of the Barcelona Open on Thursday (x denotes seeding):
Fabio Fognini (ITA x13) bt Rafael Nadal (ESP x2) 6-4, 7-6 (8/6)
Kei Nishikori (JPN x1) bt Santiago Giraldo (COL x15) 6-2, 6-1
Roberto Bautista Agut (ESP x7) bt Pablo Cuevas (URU x10) 7-6 (7/5), 6-2
David Ferrer (ESP x3) bt Elias Ymer (SWE) 6-3, 6-4
Martin Klizan (SVK x14) bt Victor Estrella Burgos (DOM) 6-4, 6-3
Pablo Andujar (ESP) bt Feliciano Lopez (ESP x5) 6-3, 6-4
Philipp Kohlschreiber (GER x12) bt Benoit Paire (FRA) 6-4, 7-6 (8/6)
Tommy Robredo (ESP x9) bt Marcel Granollers (ESP) 6-2, 6-2