Polish qualifier Jerzy Janowicz saved a match point before upsetting Andy Murray 5-7, 7-6 (4), 6-2 in the third round of the Paris Masters on Thursday.
Murray, the Olympic and US Open champion, served for the match at 5-4 in the second set, but totally lost his composure and the ensuing tiebreaker as the 69th-ranked Janowicz drew level.
"I needed to focus well on my serve. I did that for the most part, and then when I served for the match I didn't play a particularly good game,'' Murray said.
"He probably gained some confidence from that and played a good tiebreak, played aggressive. He hits a very flat ball, so when he's hitting it well it comes through the court a lot.''
The loss by third-seeded Murray came a day after second-seeded Novak Djokovic's exit to Sam Querrey on Wednesday.
It was also the third straight match Murray has failed to convert match points - he squandered two against Milos Raonic in the Japan Open semi-finals and five against Djokovic in the Shanghai Masters final.
"I have to make sure I tighten that up next week (at the World Tour Finals in London) if I get that opportunity,'' Murray said.
"Make sure I don't let it happen at the 02 (arena).''
With Roger Federer and Rafael Nadal not playing in Paris, none of the Big Four are left. Fifth-seeded Tomas Berdych reached the last eight earlier, while fourth-seeded David Ferrer was playing later.
Janowicz had the momentum after controlling the tiebreaker and broke Murray twice in the deciding set as he raced to 5-1.
"He's maybe a little bit more unpredictable than a few of them from the back of the court,'' Murray said.
"He tried a lot of drop shots and went for winners when he was out of position that maybe some of the others don't.''
Serving for the match, Janowicz saved three break points and secured the win on his second match point with a forehand winner. He slumped to the ground and broke down in tears as he held his head in his hands.
It was only his second match against a top-10 player - the first was against Murray in the 2009 Davis Cup.
As he did back then, Murray looked to be coasting to victory at the Palais Omnisports.
Serving for the match, Murray started to get flustered and his temper got the better of him as he smacked his hand against his forehead and then muttered to himself after Janowicz saved a match point. Two unforced backhand errors from Murray then helped Janowicz break for 5-5.
"I missed groundstrokes. I need to make sure I'm a little bit sharper when I'm in those positions than I have been the last few weeks,'' Murray said.
"Probably takes a bit more focus and, you know, just solid tennis rather than doing anything silly and playing sloppy shots.''
Janowicz clinched the tiebreaker when he returned Murray's weak second serve with an exquisite drop shot that Murray patted into the net.
Earlier, Berdych recovered from a poor first set to beat Kevin Anderson of South Africa 1-6, 6-3, 6-4.
The Czech was overpowered by Anderson's serve and strong defence in the first set, where Anderson hit six aces and broke Berdych twice, while saving all three break points he faced.
"The way that Kevin started was incredible. I had no chance, everything went on his side,'' Berdych said.
"But I still had the hope and belief I could make it.''
He next plays Gilles Simon of France, who advanced without hitting a ball after Kei Nishikori of Japan pulled out because of a recurrence of his right ankle injury.
With so many big names out of the way, Berdych is in a strong position to add to his 2005 title at the Bercy arena.
"It's a really new role to be (a favourite) in the tournament,'' Berdych said.