Alex de Minaur has bowed out of the prestigious Miami Open in a rollercoaster fourth-round loss to big-serving Italian Matteo Berrettini.

De Minaur missed a swag of chances to force a deciding third set in a 6-3 7-6 (9-7) defeat at tennis's so-called fifth major.

In a tense finish, Australia's 10th seed was unable to convert any of six set points but saved four match points before finally succumbing on the fifth as Berrettini advanced to the quarter-finals in two hours neat on Wednesday (AEDT).

De Minaur looked on track for another signature comeback win after having Berrettini down 4-5 and love-40 in the second set.

But the former Wimbledon runner-up rallied, winning seven consecutive points, before fighting back again from 3-6 down in the tiebreaker to deny de Minaur a tour-best 18th win of the year.

De Minaur's exit killed off the prospect of an all-Australian quarter-final with Adam Walton, the qualifying lucky loser who later lost his last-16 battle anyway, 6-3 7-5 to American third seed Taylor Fritz.

Despite their departures, de Minaur is set to return to the world's top 10 next week, while Walton will climb to a fresh career-high ranking of No.85.

Six-time Miami Open champion Novak Djokovic, meanwhile, ousted Berrettini's countryman Lorenzo Musetti 6-2 6-2 to march to within three wins of a record-extending 41st Masters 1000 crown.

The 37-year-old Serbian superstar also edged to within three victories of a milestone 100th tour-level title in a statement showing in front of Serena Williams and Juan Martin del Potro, who watched from Djokovic's courtside box.

"I was starstruck," said Djokovic, the fourth seed this year.

"It was amazing to see first 'DelPo', obviously a long-time friend and a rival, so happy to have him around and get his support from the box.

"It was amazing, the first time to have DelPo in the box, so I want to thank him really for coming.

"And Serena, that was a surprise. I didn't know. Actually, when I had that down-the-line passing shot, I pointed to her and asked her whether it was okay.

"She kind of said, 'Yeah, it was fine'. If Serena says it was fine, then it was amazing by everyone else's standards. So yeah, great to have them."

Next up for fourth-seeded Djokovic is American Sebastian Korda, a 6-4 2-6 6-4 winner over veteran Frenchman Gael Monfils.

Korda lost a thrilling three-setter to the 24-time grand slam champion in their only previous meeting in the Adelaide International final in 2023.

Argentine Francisco Cerundolo upset three-time major finalist Casper Ruud 6-4 6-2 to reach the quarter-finals for the third time in four years.

Cerundolo never faced a break as he pummelled the fifth-seeded Norwegian with six aces and 21 winners, setting up a meeting with world No.15 Grigor Dimitrov, who defeated home hope Brandon Nakashima 6-4 7-5.

An ailing Tomas Machac withdrew from his scheduled fourth-round clash with fellow Czech Jakub Mensik.

Mensik will play either German top seed Alexander Zverev or Frenchman Arthur Fils for a place in the semi-finals.

Zverev or Fils will complete the quarter-final line-up on Thursday.