At an altitude of 1892 meters, Kämna (Bora) sprinted ahead of Lopez (Trek), his last companion in a breakaway launched from afar.
The peloton of favorites, including Briton Simon Yates, Ecuadorian Richard Carapaz and Frenchman Romain Bardet, arrived more than two and a half minutes late.
Kämna, 25, won the 6th victory of his career.
He had already won the Tour de France 2020 by winning the Villard-de-Lans stage.
The wearer of the pink jersey, the Dutchman Mathieu van der Poel, stalled on the first ramps of the long ascent of Etna (22.8 km at 5.9%).
Main victims of the day, the Dutchman Tom Dumoulin, winner of the Giro 2017, was distanced almost 10 kilometers from the summit.
Subsequently, another former winner, the Italian Vincenzo Nibali, also let go.
During this sunny day, the Giro was deprived on its fourth day of one of the outsiders, Miguel Angel Lopez, who gave up in the first hour of the race.
Third in the 2018 edition, the Colombian climber suffered from left hip pain.
On Wednesday, the race remains in Sicily for the 174 kilometer long 5th stage between Catania and Messina.
A pass is located before the halfway point but the final is favorable to sprinters.
© 2022 AFP