Dan Martin went solo to claim a maiden Giro d'Italia stage victory and leader Egan Bernal finally showed signs of weakness on a brutal final climb.
Martin moved away on his own just over 10 kilometres from the end of the gruelling 193km stage 17 from Canazei to Sega di Ala and there was no catching the Irishman.
The Israel Start-Up Nation rider was the only member of a breakaway group, which had included eight men at one point, who was not reeled in.
Martin's victory completed a Grand Tour clean sweep, with two Tour de France and Vuelta a Espana successes already to his name.
He finished 13 seconds ahead of Joao Almeida and crossed the finishing line 30 seconds before Simon Yates, who showed he is still very much up for the fight in the battle for the maglia rosa.
Bernal had won stage 16 in impressive fashion on Monday, but looked in trouble on steep sections on a long final ascent in the maglia rosa.
The INEOS Grenadiers had to grit his teeth as Yates shot up the mountain in front of him, yet is still in a strong position with an advantage of two minutes and 21 seconds over Damiano Caruso.
Yates moved into third place overall, with three minutes and 23 seconds to make up on the 2019 Tour de France champion from Colombia.
Bernal has been troubled by a lingering back injury and had to really dig in, with great support from team-mate Daniel Martinez, as Yates made a statement in the final week of the race.
Hugh Carthy dropped off the podium to fifth as he suffered late on another hugely challenging day.
STAGE RESULT
1. Dan Martin (Israel Start-Up Nation) 4:54:38
2. Joao Almeida (Deceuninck–Quick-Step) +00:13
3. Simon Yates (Team BikeExchange) +00:30
4. Diego Ulissi (UAE Emirates) +01:20
5. Damiano Caruso (Bahrain Victorious) +01:20
CLASSIFICATION STANDINGS
General Classification
1. Egan Bernal (INEOS Grenadiers) 71:32:05
2. Damiano Caruso (Bahrain Victorious) +02:21
3. Simon Yates (Team BikeExchange) +03:23
Points Classification
1. Peter Sagan (Bora-Hansgrohe) 135
2. Davide Cimolai (Israel Start-Up Nation) 113
3. Fernando Gaviria (UAE Emirates) 110
King of the Mountains
1. Geoffrey Bouchard (AG2R Citroen Team) 180
2. Egan Bernal (INEOS Grenadiers) 109
3. Dan Martin (Israel Start-Up Nation) 79