Saxo Bank rider Nuyens took victory on home soil in Belgium after the peloton, containing a host of top sprinters, failed to close down a slim advantage held by the escapees over the final 20km in the opening race of the Flemish cycling week.
Garmin's American sprinter Tyler Farrar led the peloton over the line in third place followed by Matthew Hayman with 2007 winner Tom Boonen back in ninth.
Rob Goris (Willems Verandas), Frederic Amorison (Agricole), Tom Veelers (Skil) and Dries Hollanders (An Post-Sean Kelly) attacked early on the 203km trek from Roeselare and still had a 5:40 lead with 70km remaining.
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Amorison attacked the group as they crossed the Oude Kwaremont inside the final 35km, the 12th of the 16 climbs on the mini Tour of Flanders featuring a number of difficult cobbled ascents, and was joined by Goris.
Nuyens and Team Sky's Thomas bridged the gap with 20km remaining, with Goris and then Amorison losing contact, but the duo never held a lead over the peloton of more than 30 seconds.
Leopard Trek seemed to have organised the chase and narrowed the gap to inside 15 seconds and Thomas and Nuyens were dangling out in front with a slender lead as they went under the Flamme Rouge.
The Welshman led out the sprint but 30-year-old Nuyens, who won the Tour of Britain in 2005 as a Quick Step rider and was second in the 2008 Tour of Flanders whilst with French team Cofidis, jumped off his wheel to take victory in the 66th edition of the race.
The Flemish cycling week continues with Gent–Wevelgem this weekend before the Three Days of De Panne and the Tour of Flanders.
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