Stage 4 was tougher than many expected, with riders failing to cope with the pace up the Via del Fortino. The highest profile riders to lose time were 2012 Giro d'Italia winner Ryder Hesjedal (Trek-Segafredo) and last year's fourth place finisher Andrey Amador (Movistar) both conceding 43 seconds to stage winner Diego Ulissi (Lampre-Merida).
Hesjedal spoke after the stage. Whilst disappointed, he was far from distraught with the time loss.
"It was fast all day and definitely in the last 80 kilometres or so it was full-on with shorter, complicated climbs," said Hesjedal.
"Even on the last climb I was right there and I could see the front and just in the last couple of switchbacks before getting onto the highway a bunch of guys let the wheels go and then all of a sudden no one wanted to help (close the gap).
"I was a bit isolated and a few seconds at the top turned into 35 in seven kilometres. That's the frustrating part, but what can you do? It was a complicated stage near the end. But I feel that we rode well and did everything right and then still at the end to still lose time eats at you a little bit more.
"But, the race is long so you can't get too worried about it. If I have the legs I know I can have in the second half of the Giro, then today won't matter. And if I don't have the legs I know I can have, well... today won't matter."
"You don't want to lose time ever, but you have to realize the race is long and it can definitely be worse," said Hesjedal.
"It was worse the last two years at this stage of the race, but it's more frustrating when you know that you have good legs. But this is also the plus side knowing that I feel good, especially when compared to a couple of weeks ago."
Time will tell whether this early faltering will be felt by the Canadian later in the race or if he can overcome this hiccup and return to the battle for pink.