Lennard Kämna (BORA-hansgrohe) and Juan Pedro López (Trek-Segafredo) were part of a 14-strong group that emerged in the early part of the stage.
López hunted down lone attacker Stefano Oldani (Lotto Soudal) on the steep slopes of Mt Etna, and set off up the road by himself, stretching out a lead to a group of chasers including Kämna to 30 seconds.
Kämna attacked from behind, reaching López as the trees gave way to the exposed volcanic rock closer to the summit. The pair went into the finale together with López sitting on, but it was Kämna who emerged the stronger, aided by a tight final corner where López took the wrong line and touched the German’s back wheel, losing a lot of speed to avoid crashing allowing Kämna time to celebrate ahead of the line.
"I stayed for as long as possible in the main part of the breakaway, because it was windy and I didn't feel totally confident about staying out there alone," Kämna said.
"But then the gap on López was getting too big, I realised that if I was going to try and reach him I had to make a move, otherwise my chance would be gone. So I'm very happy it worked out."
Kämna had winning form coming into the race from the Tour of the Alps, giving him confidence heading into the Giro d'Italia, he had already almost claimed a victory on the final ascent to Visegrád on Stage 1 where he attacked late and led into the final kilometre.
"Day by day, I was getting better and better in the (Tour of the) Alps, feeling much better on stage 5, than even when I won (Stage 3). I was on a higher level than I expected myself."
"This Giro is definitely not about the overall for me, I just want to hunt for some more stages," he said when asked about overall ambitions. "Although I also want to support the team leaders as well as possible.”
López hit his handlebars in frustration but had the consolation of claiming the race leader’s pink jersey. He how leads Kämna by 39 seconds, with Simon Yates (Team BikeExchange-Jayco) the first of the major general classification contenders at a minute and 42 seconds in arrears.
Rein Taaramäe (Intermarché-Wanty-Gobert) was the strongest of the rest of the break and finished third at 34 seconds and is also third overall at 58 seconds adrift.
The peloton had a sedate day in the saddle until the final climb, the main incident of note when a race motorbike crashed in the middle of the bunch while trying to pass the peloton. All riders were able to pick themselves up and continue the race.
Simon Yates also crashed, having to drop back to the race doctor and seek mid-stage medical attention for his knee, though he finished with the best of the riders from the peloton at the finish.
The pace was upped significantly by INEOS Grenadiers on the final climb, with a succession of riders reducing the main bunch significantly.
With 8 kilometres to go, Tom Dumoulin (Jumbo-Visma) was distanced, unable to follow on the steepest gradients. He finished nine minutes and ten seconds down on Kämna, marking the end of his GC hopes in this year’s Giro. With teammate Tobias Foss also losing just under four minutes on the day, it was a poor day for Jumbo-Visma’s overall ambitions.
Soon after Vincenzo Nibali (Astana Qazaqstan) was dropped, while fellow pre-race contender Guillaume Martin (Cofidis) also lost contact, both would go on to lose four minutes.
There were no other major surprise losses from the main bunch as the gradients became shallower towards the top of the climb, with Richard Carapaz (INEOS Grenadiers) leading the 17-rider group over the finish line.
Australians Richie Porte (INEOS Grenadiers), Jai Hindley (BORA-hansgrohe) and Lucas Hamilton (Team BikeExchange-Jayco) were all present in the final riders, with Porte sitting the best on the general classification, ninth overall, two minutes and four seconds behind López.
The Giro d’Italia continues with Stage 5, expected to be one for the sprinters, but with a big climb mid-stage that may make a strong breakaway fancy their chances. The stage starts on SBS On Demand at 7.20pm AEST, with the SBS broadcast starting at 11pm AEST. WA viewers can tune in on SBS VICELAND from 9pm AWST.