Movistar's Giro d'Italia contender Richard Carapaz won stage four on Tuesday as a mass fall in the peloton seven kilometres from the finishing post cost 2017 champion Tom Dumoulin a devastating four minutes in the overall standings.
The fall saw a small group of eleven riders get away from the peloton, including overall leader Primoz Roglic and two of his chief contenders to win the Giro, Britain's Simon Yates and Astana's Miguel Angel Lopez.
Ecuador's Carapaz made a long-range sprint for the line from over 400 metres out with only Australia's Caleb Ewan and UAE's Diego Ulissi capable of challenging and ending second and third respectively.
Roglic, a former ski jumper, finished two seconds behind this trio, gaining 16 seconds on all his chief rivals for the 2019 title.
Dutchman Dumoulin freewheeled most of the way to the finishing post after his fall with blood streaming from a knee, with his chances of winning the title in tatters.
Wednesday's fifth stage is a short 140km run from Frascati, just south of Rome, to Terracina where a 1.5km home straight should provide a perfect platform for a spectacular sprint finish.