Andrey Rublev, Russia's world No.6, Muscovite born and resident, has been knocked out of his hometown tournament, the Kremlin Cup, by Adrian Mannarino.
The Frenchman, ranked 51 in the world and a decade older at 33, lost the first set but rallied to win 5-7, 7-6 (7-4), 6-3.
The match was a repeat of the event's last final, in 2019, which was the pair's only previous meeting. On that occasion Rublev won 6-4, 6-0.
Mannarino completed victory in a ten seconds under two-and-a-half hours. He will now meet Ricardas Berankis, a Lithuanian lucky loser, in the quarter-finals.
Berankis, a finalist in Moscow in 2017, brushed aside Argentina's Federico Coria 6-2, 6-1.
No.4 seed Filip Krajinovic is also out. The Serbian lost 6-3, 6-4 to Pedro Martinez, of Spain.
Martinez will now meet Marin Cilic, a two-time winner and the only remaining seed in the top half of the draw.