Briton Tao Geoghegan Hart won his first Grand Tour stage to climb to fourth place overall at the Giro d'Italia.
It was a fifth stage win of the race for Ineos Grenadiers.
Wilco Kelderman was second to stay second overall, 15 seconds behind race leader Joao Almeida, who has lost time on both significant uphill finishes.
Climbing specialist Geoghagen Hart now trails Almeida by two minutes, 57 seconds with four of the remaining six stages in the mountains.
Almeida is a bit of an unknown quantity, given the 22-year-old is in his first season and racing in his first Grand Tour.
He took the race leader's pink jersey on stage three and is yet to relinquish it but he is realistic in his expectations.
"I'll give my best," Almeida said after Sunday's 153km race from Base Aerea Rivolto to Piancavallo, north of Venice. "I know it will be almost impossible to bring the maglia rosa to Milan, but we will try and give everything we have.
"There are still six stages to go and I've never done anything as long as this, but so far, the feeling is good. I'm excited to see how far I can go."
He was not the only general classification contender to lose significant time on stage 15, with two-time winner Vincenzo Nibali finishing more than 90 seconds back and he is now more than three minutes behind Almeida.
Kelderman, who is racing in his 11th Grand Tour and has a best finish of fourth at the 2017 Vuelta a Espana, would now appear to be the favourite as the riders enjoy a rest day on Monday.
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An emotional first win
Geoghegan Hart, 25, powered past Sunweb's Kelderman for the win in the final few metres of the category one summit finish, after the Dutchman's team-mate Jai Hindley had paced everyone up the long final climb.
Geoghegan Hart dedicated the victory to Nico Portal, Ineos' sporting director who died of a heart attack aged 40 in March this year.
"This is something incredible for me. I don't know about [the general classification], I haven't seen the results - but crossing the line first is something truly incredible.
"This one is for Nico Portal. We lost him this spring and it's been really difficult for the team - this season has had great highs and lows, in the Tour [de France] and for me personally, and also in this race.
"We just have to foster the Grenadier spirit in this team and keep fighting back like we know we can."
Is Geoghegan Hart a serious contender?
Despite his young age, the east Londoner has long been a part of the Ineos/Sky set-up as a domestique, but like so many of the team's riders he is capable of winning the general classification in stage races.
However, it appeared Ineos would have to settle for trying to win stages for a second Grand Tour in succession when race favourite Geraint Thomas was forced to abandon with a fractured pelvis.
The Welshman crashed when a discarded drinks bottle became lodged under his front wheel.
But this has been one of the most unpredictable Giros for years, and after spending at least a week more than three minutes down, Geoghegan Hart finds himself in contention.
His biggest strength is climbing, and as the race heads for a final week's racing in the ever-colder Italian Alps he stands a good chance of gaining time, especially on leader Almeida who is thought to be more effective in time trials, although the final stage of the race is an individual time trial.
Kelderman is clearly in a great position, given he is two minutes, 42 seconds ahead of both his third-placed team-mate Hindley and Geoghagen Hart, but Pello Bilbao of Bahrain-McLaren, Rafal Majka of Bora-Hansgrohe and Trek-Segafredo's Nibali are also in contention.
A final week of controversy?
After a rest day on Monday, the three-week race is heading into it's final week in the Italian Alps, where it was feared adverse weather could cause stages to be cut short or even cancelled.
Weather forecasts are currently reasonably favourable if cold in places, but organisers are wary the coronavirus could also play a part.
All riders and staff will now be tested for a third time during the race after last week's rest day tests produced three positive Covid-19 results for riders - including Britain's Simon Yates - and several other team members, causing Mitchelton-Scott and Jumbo-Visma to pull out of the race.
Tuesday's stage is an undulating 229km race from the north eastern city of Udine to San Daniele del Friuli.
Stage 15 result
1. Tao Geoghegan Hart (GB/Ineos Grenadiers) 4hrs 58mins 52secs
2. Wilco Kelderman (Ned/Sunweb) +2secs
3. Jai Hindley (Aus/Sunweb) +4secs
4. Joao Almeida (Por/Deceuninck-Quick-Step) +37secs
5. Rafal Majka (Pol/Bora-Hansgrohe) +1min 2secs
6. Patrick Konrad (Aut/Bora-Hansgrohe) +1min 29secs
7. James Knox (GB/Deceuninck-Quick Step) +1min 36secs
8. Pello Bilbao (Spa/Bahrain-McLaren) +1min 36secs
9. Jakob Fuglsang (Den/Astana) +1min 36secs
10. Vincenzo Nibali (Ita/Trek-Segafredo) +1min 36secs
General classification after stage 15
1. Joao Almeida (Por/Deceuninck-Quick-Step) 59hrs 27mins 38secs
2. Wilco Kelderman (Ned/Sunweb) +15secs
3. Jai Hindley (Aus/Sunweb) +2mins 57secs
4. Tao Geoghegan Hart (GB/Ineos Grenadiers) 2mins 57secs
5. Pello Bilbao (Spa/Bahrain-McLaren) +3mins 10secs
6. Rafal Majka (Pol/Bora-Hansgrohe) +3mins 18secs
7. Vincenzo Nibali (Ita/Trek-Segafredo) +3mins 29secs
8. Domenico Pozzovivo (Ita/NTT Pro Cycling Team) +3mins 50secs
9. Patrick Konrad (Aut/Bora-Hansgrohe) +4mins 09secs
10. Fausto Masnada (Ita/Deceuninck-Quick-Step) +4mins 12secs
14. James Knox (GB/Deceuninck-Quick Step) +8mins 55secs