Andre Agassi was beaten at the Nasdaq-100 Open for the first time in four years on Tuesday, losing 6-2, 7-6 to Argentina's Agustin Calleri in the fourth round.
Agassi has won the title in Miami six times, including the last three years, and Calleri's victory snapped a 19-match winning streak the American had compiled at the tournament.
His last defeat at the Crandon Park Tennis Centre was in the 2000 semi-finals, when he was beaten by Gustavo Kuerten.
On Tuesday, Agassi lost the first set amid a blitz of winners and found himself in even deeper trouble when he twice went a break down in the second set.
The fourth seed retrieved both breaks and had set points at 5-4 on the Calleri serve before the Argentine sealed the match in the tie-breaker.
"He was just playing too good for a long stretch of time out there," Agassi said.
"I raised my level to hang in there but it just wasn't enough. The guy was just making me play great tennis and I wasn't coming up with it."
Calleri next lines up against Vince Spadea after the 29-year-old beat ninth seed Paradorn Srichaphan of Thailand 5-7, 6-3, 6-2, sending a message to watching U.S. Davis Cup captain Patrick McEnroe.
McEnroe selected Mardy Fish over Spadea for the U.S.'s quarter-final tie against Sweden next week, claiming the latter's age was against him despite a title win in Scottsdale three and a half weeks' ago and a good performance here.
However, Andy Roddick remains favourite for the title after his 6-3, 6-3 fourth round win over Argentine Guillermo Canas.
Roddick took just over an hour to carve out the comprehensive victory, which came with the help of the 12 aces.
He plays Carlos Moya in the quarter-finals after the former French Open champion beat fellow Spaniard Tommy Robredo 6-3. 6-3.
Fernando Gonzalez ended the hopes of another Spaniard, Rafael Nadal. Gonzalez beat the 17-year-old conqueror of top seed Roger Federer 7-6, 4-6, 6-2.
Another Argentine, Guillermo Coria, narrowly escaped defeat in his fourth-round match, clawing his way back from 2-5 down in the third set to beat French qualifier Julien Benneteau 7-6, 2-6, 7-5.
"Even at 5-2 I was thinking about how to fight my way out of it," the third seeded Coria said.
"You don't get to the top of the game without being able to come through tough situations."
Coria next plays Nicolas Kiefer and although the former top 10 player from Germany has fallen on hard times in recent years, he is enjoying something of a return to form in Miami.
Having knocked out sixth seed Rainer Schuettler earlier in the week, Kiefer beat 12th seed Sebastien Grosjean 6-4, 6-2.
SERENA BLITZ
In the women's draw, Serena Williams blasted her way through to the semi-finals with a 6-0, 6-1 victory over unseeded American Jill Craybas.
Williams, playing her first tournament following an eight-month injury lay-off, needed just 55 minutes to demolish her 29-year-old opponent.
"I'm definitely getting more consistent," said Williams, who next plays Eleni Daniilidou of Greece after the 25th seed eased past Croatian Karolina Sprem 6-1, 6-3.
"I'm excited to be back out there. It's everything I thought it would be and more. I feel really excited and happy and blessed that I can still play."