Nairo Quintana (Movistar) tightened his grip on the Vuelta a España red jersey by coming second on Stage 15, three seconds behind Gianluca Brambilla (Etixx-QuickStep), stretching his lead over Chris Froome (Sky) in the general classification from 54 seconds to 3:37.
Orica-BikeExchange's Esteban Chaves remains third, a further 20 seconds behind Froome, having finished the stage 47 seconds ahead of Froome after riding most of the stage with the 2016 Tour de France winner.
Quintana and Froome had completed the last two stages together but it quickly became clear that the stage from Sabinanigo to Sallent de Gallego would be different.
Quintana and Alberto Contador (Tinkoff) formed an alliance and launched several early attacks before forming a breakaway group within the first 10km of the 118.5km stage.
Froome was left in the peloton with Chaves and their group kept slipping further behind the breakaway.
Three-time Vuelta winner Contador eventually trailed off towards the finish, coming home 34 seconds behind Brambilla in sixth place.
“It went way, way better than we expected, Quintana said. "To be honest, we were thinking more about taking some moves in the finale.
"However, you never really know what’s gonna happen. It turned out to be a really great stage in the least of expected ways.
"We opened bigger gaps here than in yesterday’s big mountains. At the start, a split was created into a lumpy section, full of twists and different slopes where our bodies suffered a lot after yesterday’s efforts.
"We struggled, yet we kept focus, went ahead with Alberto and our teams cooperated well.
“I was screaming to them (his Movistar team-mates) ‘Full gas, full gas, we’re leaving Froome behind', and then, the rest of the team, took care of what was going on behind.
“We opened a gap, we kept it high and at the final climb, I gave everything to keep Chris well behind. Fortunately, I’ve opened the gap I considered I needed before the TT.
“I just hope I can keep it and stay strong until Madrid. We will remain cautious, yet we know we’ve got a great team."
Stage 16 runs 156km from Alcaniz to Peniscola ahead of the second and final rest day.