Thomas Voeckler successfully defended the race leader's yellow jersey on Bastille Day, but defending champion Alberto Contador lost time to his overall rivals on the first mountain stage of the 2011 Tour de France.
Samuel Sanchez (Euskaltel-Euskadi) finished ahead of Jelle Vanendert (Omega Pharma-Lotto) and Frank Schleck (Leopard Trek), who were second and third respectively, on the 211-kilometre 12th stage from Cugnaux to Luz-Ardiden in the Pyrenees.
Ireland's Nicolas Roche finished in 17th place on the stage, in a time of six hours, three minutes and 17 seconds, two minutes and two seconds slower than Sanchez.
The result saw the La Mondiale rider climb to 10th place overall, four minutes and 57 seconds behind Voeckler.
The overall favourites played a watchful role, but Frank Schleck's move enhanced his position, while Contador (Saxo Bank-SunGard) struggled in the final stages, trailing in eighth, 43 seconds behind Sanchez.
It was a race within a race as Contador (Saxo Bank-SunGard), Andy Schleck, Frank Schleck (both Leopard Trek) and Cadel Evans (BMC Racing) marked each other up the Tour's first hors categorie (beyond category) climbs - the Col du Tourmalet and the ascent to Luz-Ardiden.
But Contador, who began the day four minutes 7 seconds behind Voeckler (Europcar) saw his resistance broken in the final 500metres of the final climb.
After an Andy Schleck attack and two from Frank Schleck, a third from the older Schleck brother saw him break clear.
Frank Schleck closed in on Sanchez and Vanendert, while behind him Evans, Ivan Basso (Liquigas) and Andy Schleck continued to push at a high tempo.
Frank Schleck finished 10 seconds behind Sanchez and three behind Vanendert, while Basso was fourth, Evans fifth and Andy Schleck sixth, all three 30 seconds behind Sanchez - but crucially 13 seconds ahead of Contador.
Damiano Cunego (Lampre-ISD) was seventh, five seconds behind Basso's group, before Contador crossed the line in eighth, followed by Voeckler in ninth.
Voeckler now leads overall from Frank Schleck by 1min 49secs, with Evans third, 2:06 behind.
Andy Schleck lies fourth, 2:17 adrift, with Basso fifth at 3:16, Cunego sixth at 3:22 and Contador seventh, 4:00 adrift of Voeckler.