Fabian Cancellara will miss the remainder of cycling's spring classics after fracturing his lower back at the E3 Harelbeke race in Belgium.
The 34-year-old Trek Factory rider was one of the favourites to win the Tour of Flanders and Paris-Roubaix.
"It all happened so fast," the Swiss said. "I flew over a couple of riders and landed in a pile of bikes. I fell so hard, and felt pain everywhere."
Team Sky's Geraint Thomas became the first Briton to win the race.
Cancellara, who has won three times at both the Tour of Flanders and Paris-Roubaix, was one of several riders to crash when a discarded water bottle caused chaos in the peloton. He abandoned the race a few kilometres afterwards.
Trek Factory Racing later added on Twitter: "X-rays have confirmed the worst: Two fractures of vertebrae in lower back for Cancellara means no spring campaign."
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Belgium's Tom Boonen, who has won the Tour of Flanders four times and the Paris-Roubaix three times, will also miss both races with a shoulder injury.
The absence of two former champions will aid Team Sky rider Sir Bradley Wiggins, who is aiming for success in the Paris-Roubaix.
It will be his final road race before switching to the track and bidding to qualify for the Rio 2016 Olympic Games.