Primoz Roglic (Jumbo-Visma) lit up Paris-Nice with a devastating attack that propelled him into the leader’s jersey on Stage 4.
The Slovenian launched on Col de Durbize with three kilometres remaining, quickly overtaking the weary legs up the road and soaring away to win.
Previous overall leader Michael Matthews tried to counter-attack but against a GC specialist his threat was quickly dismissed.
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Roglic will pull on the leader’s yellow jersey on Thursday with a 35-second lead over Max Schachmann (Bora-Hansgrohe).
'A huge marker!' - Roglic takes Stage 4 victory
Roglic defended his La Vuelta title in November, less than two months after surrendering the Tour de France GC on the final competitive stage to compatriot Tadej Pogacar.
'It's beautiful' - Roglic on winning Stage 4 in his first race of the season
Meanwhile, Tao Geoghegan Hart (Ineos Grenadiers) abandoned the race after crashing with 19 kilometres remaining.
The Giro champion pressed on but, unable to bridge the gap to the leaders and suffering from his fall, eventually dropped out.
His Ineos-Grenadiers team, who had already lost Australian Richie Porte in a crash during the opening stage, said the Briton was heading to hospital "for further assessment".
"His front wheel slipped and he landed on his face, his head and his knee pretty bad and he felt a bit dizzy. So it was the right decision to stop him," Ineos-Grenadiers sports director Gabriel Rasch said.
"Landed on my head today. Thank you @INEOSGrenadiers & the medical team for putting my long-term welfare first when it was clear I wasn’t 100%," Geoghegan Hart wrote on Twitter.
Roglic was pleased with his stage four victory, saying: "I'm definitely happy about the result.
"Already yesterday was a nice one. I showed that I proved to myself that we were working good, so yeah, it's beautiful and I'm super happy that we have two wins [Wout van Aert also won at Tirreno-Adriatico] for our team today.
"t was a hard day, so it was something for me, definitely. It was beautiful that I had the legs and could finish it off.
"Definitely the goal is to have it in Nice, but yeah, we deserved it and I think we have a strong team here, so we go optimistic into the next stages. We'll do our best and we'll see what that means for the result."
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