Geraint Thomas on Tuesday pulled out of the Giro d'Italia having sustained a broken pelvis in a fall on Monday's third stage, before the fourth stage got under way.
Catania doctors said his season was over.
The 34-year-old 2018 Tour de France winner, who rides for Ineos, was one of the pre-race favourites but fell twice on Monday's stage and accumulated a 12-minute deficit from the leaders.
Despite breaking his pelvis the Welsh national hero managed to get to the finishing line, 12 minutes and 19 seconds behind winner Jonathan Caicedo of Ecuador.
Thomas has fallen on the Giro before, in 2017, on the Blockhaus in Abruzzo, when he also fell far off the lead.
The Welshman skipped this year's Tour de France to prepare for the Giro.
Thomas, who came second in last year's Tour, has won three track world championships and two Olympic gold medals.
Like older compatriot and teammate on both track and road, Bradley Wiggins, he is one of the few riders in the modern era to achieve significant elite success as both a track and road rider, with notable victories in the velodrome, in one-day racing and in stage racing.
Portugal's Joao Almeida grabbed the lead in the Giro d'Italia on the third stage on Monday.
Ecuadoran champ Caicedo broke away and won the 150km stage from Enna to Etna in Sicily, the first hilly stage on this year's course.
The big names came in way behind Caicedo apart from Denmark's Jakob Fuglsang, Poland's Rafal Majka and Sicily's own Vincenzo 'The Shark' Nibali, who managed to limit the arrears to 51".
In the general classification, Kelderman is 42" from Almeida, then Nibali at 55" and Pozzovivo at 59"; Fuglsang at 1'13", Kruijswijk at 1'15" and Majka at 1'26".
Simon Yates came in 3'26" behind the stage winner.
General classification: 1. Joao Almeida (Por) in 07h44'25" 2.
Jonathan Caicedo (Ecu) s.t. 3. Pello Bilbao (Spa) at 00'37" 4.
Wilco Kelderman (Ned) at 00'42" 5. Harm Vanhoucke (Bel) at 00'53" 6. Vincenzo Nibali (Ita) at 00'55" 7. Domenico Pozzovivo (Ita) at 00'59" 8. Brando McNulty (Usa) at 01'11" 9. Jakob Fuglsang (Den) at 01'13" 10. Steven Kruijswijk (Ned) at 01'15" 11. Rafal Majka (Pol) at 01'26" 15. Ilnur Zakarin (Rus) at 01'38" 25. Simon Yates (Gbr) at 03'46" 32. Tanel Kanger (Est) at 05'19" 53. Geraint Thomas (Gbr) at 11'17".
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