Roger Federer suffered a stunning 7-6, 2-6, 7-6 defeat by Guillermo Canas in the Sony Ericsson Open fourth round on Tuesday, the world number one's second loss to the Argentine in successive tournaments.
Second seed Rafael Nadal of Spain and third seeded American Andy Roddick made smooth progress into the final eight.
Nadal swept past Argentine Juan Martin Del Porto 6-0, 6-4 and Roddick advanced with a 7-5, 6-3 win over Spain's David Ferrer.
Canas, who snapped Federer's 41-match winning streak at Indian Wells two weeks ago, battled the Swiss defending champion for two hours 38 minutes in a riveting Stadium court duel that ended when the Argentine sealed victory with a service winner.
Back on the ATP Tour after serving a 15-month doping ban, Canas joins select company, becoming just the fifth player to record back-to-back wins over Federer who lost only two hard court matches all last season.
"I really expecting to win, it was one of those matches I shouldn't have lost," Federer told reporters. "But he's a great competitor. He played well both times and I just couldn't put him away."
Canas, world number 55, was unable to pinpoint the key to his success against a player who has been almost unbeatable since 2004, compiling a sparkling 261-16 record including 35 titles in 51 tournaments.
The 29-year-old Argentine is not without a solid tennis pedigree of his own, however, having been a top 10 player with six career wins before being handed his drug suspension.
"I don't know what it is the key to beat him, I fight for every point and I think for that I beat him," said Canas, who had to qualify for his place in the last two events.
"I think I have luck because I played very well the two matches.
"I think I played great tennis today, for me it's like a dream. To beat two weeks in a row the world number one, it's amazing.
"I don't know what I do, I just know I played very good tennis."
After losing the opening set in a tiebreak 7-2, Federer appeared to finally find his rhythm, easily winning the second set and carrying the momentum into the third to break a fading Canas at the first opportunity to go ahead 2-0.
But Canas showed his experience, refusing to buckle under the Federer's pressure and levelling the set at 3-3.
Top seed Federer had several opportunities to regain control but could not break Canas, the Argentine maintaining his perfect record against the Swiss in tiebreaks with a 7-5 success.
"I was in almost total control for almost all the match once I broke back in the first set," said Federer.
"I thought it was a great match, so it was disappointing to lose.
"He dug deep and played well, I was just not in the end very happy with the way things went. I could have won but I didn't do it."
Canas next meets sixth seed Tommy Robredo of Spain in the final eight while Federer will get an early start to his claycourt preparations for the French Open.