Rigoberto Urán and Sergio Henao both battled hard on the queen stage of the Giro d'Italia to continue their superb Grand Tour showings.
The duo finished eighth and ninth on the mythical Passo dello Stelvio after slipping back late on from a group of elite contenders.
Up ahead Thomas De Gendt produced a career-defining ride to take victory on the highest mountain-top finish in Grand Tour history the Vacansoleil-DCM rider finishing 55 seconds ahead of his closest rival to vault up to fourth in the overall standings.
Damiano Cunego (Lampre-ISD) and Mikel Nieve (Euskaltel-Euskadi) were next home, unable to live with the accelerations of De Gendt who, after attacking first on the steep ramps of the Mortirolo, pushed onwards again on the lead-up to the 2,757-metre final climb.
With the breakaway riders able to build up a sizeable advantage both Urán and Henao slipped back on the day, Uran dropping to seventh while Henao was nudged out of the top 10. Both men still remain firmly atop the white jersey standings.
Henao, in his first Grand Tour, put in another superbly assured performance, benefitting from high altitude training in Colombia to help his compatriot Urán in the final kilometres.
Behind De Gendt the leading contenders scrambled to cover off the threat up the road, Ryder Hesjedal (Garmin-Barracuda) forced to push onwards after team-mate Christian Vande Velde had buried himself on the lower slopes of the Stelvio.
On the snow-lined roads Michele Scarponi (Lampre-ISD) was the first to attack, the 2011 winner pushing onwards only to be overhauled by race-leader Joaquim Rodriguez, the Katusha man re-extending his lead after taking fourth.
The Spaniard's late surge was to the detriment of Mark Cavendish as the Brit, who finished comfortably in the gruppetto, was forced to relinquish the red points jersey by a single point to the climber.
With just the final Milan time trial remaining, Rodriguez holds a 31-second advantage over Hesjedal, the Canadian still sitting in the box seat with his superior time trialling ability.
Scarponi clung onto the final step of the podium with De Gendt threatening just 27 seconds back heading into the 30-kilometre test.
Earlier 17 riders went clear in the day's break on the Passo del Tonale, a significant move with the top four men on the GC all having riders in the break.
Oliver Zaugg (RadioShack-Nissan) and Matteo Carrara (Vacansoleil-DCM) pushing on up the brutally steep slopes of the Mortirolo, with Carrara soon to be joined by team-mate De Gendt.
In a surprise move, Rodriguez put in a speculative attack, firing a warning shot to test the legs of his rivals, yet with 61km to go the Spaniard knocked off the move and resumed tempo.
Behind a gruppetto including Cavendish began to form heading out of Tirano at the foot of the Mortirolo after what had been a big effort to stay in up to that point.
Sitting eighth coming into the stage, De Gendt sprung clear alongside team-mate Matteo Carrara, eventually linking up with Cunego and Nieve to drive out a dangerous advantage.
Behind the favourites began to look at each other and the gap rolled out to around four minutes before order was temporarily restored, yet De Gendt kicked on again, taking a further minute to cement his insurmountable advantage.
After being pulled back from the break Vande Velde set about riding on the front in service of Hesjedal on the lower slopes of the Stelvio but the gap held steady.
The race will be decided on Sunday in a shoot-out between Rodriguez and Hesjedal with the winner taking home the maglia rosa in Milan.
Despite the stage not producing the result the team would have liked, Sports Director Nicolas Portal praised the effort the team put in on an incredibly tough day.
He said: “The guys did a good ride to limit their losses at the end after being up front the whole day. Sergio was a bit stronger than Rigoberto on the day. He tried to follow the attack of Scarponi with 3km to go but the effort saw him on the limit.
“In the end we have lost spots on GC but the guys put in a big effort. The time gaps to the main favourites were not too bad in the end for a stage of this magnitude. De Gendt was too strong today. It was a brilliant ride from him so you have to say chapeau.
“Of course it is disappointing to lose the red jersey this close to the end. The team has worked so hard all race and we can be proud of the effort we’ve put in.”