Germany's Matthias Kessler broke free in the final stages to win the 216.5-km third stage from Esch-sur-Alzette in Luxembourg to Valkenburg.
The T-Mobile rider surged on the ascent of the Cauberg and crossed the line about 50 metres ahead of his Australian team mate Michael Rodgers.
Daniele Benati of the Lampre team was third. Belgian World champion Tom Boonen finished fourth and claimed the yellow jersey from Norwegian Thor Hushovd.
The stage was run in scorching heat with temperatures reaching around 35 degrees celsius and tar melting on the roads.
Alejandro Valverde of Spain, Erik Dekker of the Netherlands and Fred Rodriguez of the United States crashed and were evacuated by ambulance suffering from shoulder or collarbone injuries.
Valverde, leader of the Caisse d'Epargne team, was regarded one of the favourites to succeed seven-times winner Lance Armstrong after German Jan Ullrich and Italian Ivan Basso were withdrawn after being implicated in a doping probe in Spain.
