A persecution began between the leading group and a peloton led by five Quick-Step–Innergetic riders, including Filippo Pozzato and Servais Knaven, trying to assist Tom Boonen.

With 45 kilometres to go, while going through Mons-en-Pévèle cobblestone section, George Hincapie's steerer tube broke and he injured his collarbone, forcing him to retire from the race.

With 20 kilometres to go and riding through Camphin-en Pévèle cobblestones sector, Fabian Cancellara attacked and gained a few metres along with Vladimir Gusev over the rest of the leaders.

The difference soon increased to 20 seconds when, hitting Carrefour de l'Arbre, Cancellara began a solo effort to Roubaix after Gusev couldn't hold on the pace by the Swiss time-trial specialist.

Hoste, Van Petegem and Vladimir Gusev were initially credited with 2nd through 4th places (1'23" down), but were later disqualified by the race jury for illegally riding through a closed level-crossing.