After Monday's rest day, the 100th edition of the race resumes on Tuesday with a 181km fourth stage from Cefalu in the north of Sicily to the summit of Europe's highest active volcano.
Fernando Gaviria, another Colombian, who rides for Quick Step, will start in the pink jersey after he took the race lead from fellow sprinter Andre Greipel by winning stage three to Cagliari, Sardinia, on Sunday.
But after three days of seeing the fast men of the peloton sprinting for glory, fans get a chance to tune in for some early-race salvoes in the definitive battle for the pink jersey.
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It is the first summit finish of the race and Nibali, the winner in 2013 and 2016, expects 2014 champion Quintana to put the hammer down.
"It's inevitable that something happens, because Etna is a real challenge," Nibali said Sunday when asked about the threat from Quintana.
Nibali, also the 2015 Tour de France champion, refuted reports in Gazzetta dello Sport of tension between him and climbing specialist Quintana, who rides for Movistar.
"No, not at all," Nibali said.
But Nibali, born and raised in the Sicilian town of Messina, said he isn't racing for charity. "He races for one team and I race for a rival team, so it's only normal we're enemies," he said.
"We don't acknowledge each other that often, because we're both very concentrated and have to pay attention on the road.
"But we're both here trying to win it."
Only four stages into the race's 100th edition, the ride to Mount Etna is certain to see Gaviria, a sprint specialist who excels on the flat, hand the coveted pink jersey over to a new race leader.
After a first 55km over undulating terrain, the peloton will tackle the 32.8km climb to the summit of Portella Femmina Morta.
Rather ominously, it translates to 'Dead Woman's Door'. Thankfully, its average gradient is a manageable 4.5% on average.
After a long, winding descent, a more formidable, 17.9km ascent to Etna, where the steepest sections reach 12%, provide a far tougher challenge.
"It won't be decisive, but the stage to Etna is important because it will give me an indication of my form and an indicaton of who the real GC (general classification) contenders could be for the final week," said Quintana.
As well as Nibali and Quintana, fellow GC contenders like Steven Kruijswijk (LNL), Spaniard Mikel Landa (Sky) and Tom Dumoulin (Trek) are expected to be at the front of the peloton.
A prestigious stage win is at stake, although the responsibility of controlling the race would then fall to the team of the new pink jersey holder - demanding precious energy that could prove useful for more decisive stages in the third and final week.
Yet, with stage five finishing in his home town of Messina, Nibali has extra incentive to claim the 'maglia rosa' on Tuesday.
"I can't wait for the stage to Messina, it's my home town," he said.
By Justin Davis
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Photo: Vincenzo Pinto/AFP