Tom Dumoulin reclaimed the pink jersey after Diego Ulissi won stage four of the Giro d'Italia in Praia a Mare, with Nicolas Roche moving into the top 10.
Italian Ulissi (Lampre-Merida) won his fifth career Giro stage solo after breaking clear of a splintering peloton on the short but testing final climb late on the 200km route from Catanzaro, as the race moved to southern Italy after spending the first three days in Holland.
Dutchman Dumoulin (Giant-Alpecin) was second across the line, alongside Team LottoNL Jumbo's Steven Kruijswijk, five seconds behind Ulissi and just in front of a chasing pack of general classification contenders that included Vincenzo Nibali (Astana), Alejandro Valverde (Movistar), Roche and Mikel Landa (both Team Sky).
Roche finished 10th to move up to ninth overall, 37 seconds behind Dumoulin.
His Team Sky colleague Philip Deignan was 59th on the day, 1:11 behind Ulissi, which leaves him 69th in general classification, trailing Dumoulin by 4:52.
Etixx-QuickStep sprinter Marcel Kittel, who started in pink after wins on stages two and three, was dropped on the second and final climbs of the day and finished more than eight minutes down on the leaders as he tumbled down the GC standings.
Dumoulin, who won the opening time trial, now leads overall from Kittel's team-mate Bob Jungels and Ulissi, both 20 seconds down.
Nibali sits sixth, 26 seconds back, with Valverde seventh, 31 seconds down.
The stage contained two categorised climbs, with splits appearing after the second of them as Kittel and a handful of others were dropped before regrouping.
But it was a short, uncategorised climb 10km from home which proved decisive as Ulissi capitalised on gradients reaching 18 per cent to break clear.
The peloton splintered behind him to leave significant gaps and give the general classification another shake-up before Wednesday's stage five, a 233km test from Praia a Mare to Benevento which contains early tests before a long downhill run towards the finish.