Miguel Angel Lopez fell further behind in the battle for the Giro d'Italia pink jersey on Wednesday as Enrico Battaglin claimed victory in the hills of Sicily.
Stage five's undulating start allowed the peloton to settle into a rhythm from Agrigento, but the three categorised climbs that completed the route caused problems.
Lopez was the big loser of the pre-race general classification contenders as he was caught up in a crash inside the last 15 kilometres, the Astana rider losing another 43 seconds.
He now sits nearly two minutes behind race leader Rohan Dennis and looks unlikely to be challenging for the win in Rome later this month.
It is doubtful Battaglin will be involved then either, but he showed his climbing skills to take a superb stage win in Santa Ninfa.
The LottoNL-Jumbo rider found a last burst of energy on the 153km route to speed past Giovanni Visconti and claim his third Giro stage win.
DUMOULIN HAPPY TO SURVIVE FIRST TEST
Defending champion Tom Dumoulin was pleased to have stayed in touch with Dennis at the top of the GC after the first challenging day in the mountains.
Dumoulin managed to avoid the late pile-up and come home with the peloton, losing no time to Dennis as the teams turn their attentions to the first summit finish.
"I survived again without time loss, that's what is most important," he told the Team Sunweb website.
"These stages we don't have much to win, but a lot to lose and we haven't lost anything so that's good. [Thursday] will be really hard, it's more difficult than the other side that we did last year so we will see how it goes.
"I hope that the peloton calms down as the GC is expected to settle after tomorrow. It was two days of stress here. I didn't have good legs today but I also didn't have bad legs, hopefully that means good legs for tomorrow."
1. Enrico Battaglin (LottoNL-Jumbo) 4:06:33
2. Giovanni Visconti (Bahrain-Merida)
3. Jose Goncalves (Katusha-Alpecin)
4. Max Schachmann (Quick-Step Floors)
5. Simon Yates (Mitchelton-Scott)
1. Rohan Dennis (BMC Racing) 18:29:41
2. Tom Dumoulin (Team Sunweb) +0:01
3. Simon Yates (Mitchelton Scott) +0:17
1. Elia Viviani (Quick-Step Floors) 131
2. Sacha Modolo (EF Education First-Drapac) 55
3. Jakub Mareczko (Wilier Triestina – Selle Italia) 53
King of the Mountains
1. Enrico Barbin (Bardiani) 11
2. Marco Frapporti (Androni) 7
3. Ryan Mullen (Trek-Segafredo) 6
Time for a summit finish. And what a summit! Mount Etna will be the end point for stage six on Thursday, the infamous volcano – with gradients of six per cent – the finale to 164km of riding from Caltanissetta.