Mikel Landa's Giro d'Italia hopes vanished when he abandoned with illness early on stage 10 before Italian first-year professional Giulio Ciccone powered to victory in Sestola.
Team Sky's Landa began the day one minute 18 seconds behind overall leader Gianluca Brambilla and with high hopes of attacking on the forthcoming mountain stages, but the Spaniard fell off the back of the peloton on the first climb and quit.
On an eventful day Italian Brambilla lost the leader's pink jersey to Etixx-Quickstep team mate Bob Jungels.
Ciccone (Bardiani-CSF) broke clear on the speedy descent of Plan del Falco and held firm on the final climb towards the finish to mark his Giro debut with a stage win.
While the day belonged to the 21-year-old Ciccone, Jungels leads overall by 26 seconds from Movistar's Andrey Amador with GC contenders Alejandro Valverde and Vincenzo Nibali lurking at 50 and 52 seconds adrift respectively.
Landa, third overall last year, was expected to be challenging Valverde and Nibali over the next two weeks, but his race ended forlornly in the back of a team car.
He was clearly suffering when he fell minutes behind on the first ascent and was seven minutes adrift of the leaders when he could no longer continue.
His team doctor said later it was a case of suspected viral gastroenteritis.
Team manager Dave Brailsford had planned Sky's strategy around Landa and his withdrawal is a huge blow.
"Mikel was ill overnight but we spoke this morning and he started today's stage with the hope of being able to pull through," Brailsford said.
"It was pretty clear that the illness had badly affected him and that he wasn't going to be able to continue.
"We are really disappointed for Mikel, who was riding well and looking forward to attacking in the mountains and animating the race."
Team Sky are now down to seven riders after Elia Viviani's earlier retirement and their best hope now is to go for stage wins.