Nine others have so far been identified as injured in the Campobello region of the volcanic island, although these figures are still provisional and a search mission is underway.
Four of the injured remain in serious condition.
The tornado struck around 7 p.m. Friday night, uprooting poles, damaging roofs and blowing up trees, fire departments said on Twitter.
Speaking to an Italian newspaper The Republic, an unnamed paramedic called the disaster a “truly apocalyptic scene”
“At the moment there are two confirmed deaths, but the search is continuing and we are ensuring that there are no missing,” said the paramedic. “The tornado came from the sea and within seconds it tore apart houses and cars traveling along the coastal road. “
Among those killed in the disaster were a firefighter and an 86-year-old man, the local ANSA news agency reported.
According to the news agency, the two men died after being thrown from their respective vehicles while a dozen cars were overturned.
One victim landed on a low wall and the other on the ground.
Photos posted online show one car was completely overturned and another covered in rubble.
Several buildings were also damaged.
The mayor of Pantelleria, Vincenzo Vittorio Campo, told Sky TG24 TV that no one currently appears to be missing on the island.
Tornadoes are not common in Europe. The incident came after Sicily experienced more extreme weather conditions last month, when the island suffered a heat of 48.8C – the highest temperature on record in Europe.
The region was also engulfed by a series of forest fires, which destroyed homes and businesses.
At the time, firefighters said they had fought 500 blazes overnight in Sicily and Calabria, requiring five planes and 3,000 firefighters to contain the blazes.