Dusan Lajovic had to summon all of his resources after falling ill last week, booking a place in the Monte Carlo Masters semi-finals with a 6-4, 7-5 win over Lorenzo Sonego on Friday.
The Serb surprise could find himself in a battle with compatriot and world number one Novak Djokovic if the top seed goes past Russia's Daniil Medvedev later.
Rafael Nadal, the 11-time tournament champion, faces a quarter-final against Argentine Guido Pella.
The 48th-ranked Lajovic had reached the quarters through a Thursday upset of 2018 Roland Garros finalist Dominic Thiem, the fourth seed.
He needed just over an hour and three-quarters to see off Italian qualifier Sonego in a first-time meeting.
Lajovic broke in the penultimate game with a drop shot winner and then served out the victory against the world number 96.
There had been few expectations after falling ill prior to the tournament start.
"I was on antibiotics last week, I didn't know how I'd do," he said. "But I'm now into my first Masters semi-final.
"I've been playing my best tennis. I've done well in every match," added Lajovic, who has not dropped a set so far.
"We had some wind today, it was a struggle every game. It was not easy today.
"In the second set I got a bit tight and he began playing better.
"I'm just happy to get the win in two sets."
Lajovic and Djokovic are the first two Serbs to reach the quarter-finals together at a Masters 1000 tournament.