The German sprinter was in near the front of the chase group following lone leader Vincenzo Nibali (Bahrain-Merida) on the descent of the Poggio inside the final five kilometres of the race when he crashed along with Lotto-Soudal team-mate Jasper De Buyst.
Up until that point, Greipel had looked in good shape to contest the finish despite also crashing earlier in the feed zone and suffering an abrasion to his left leg.
Greipel said via Twitter on Sunday: "Unfortunately not the way I wanted to finish my @Milano_Sanremo. 2 crashes and the last one 4 km from the finish let our amazing @Lotto_Soudal teamwork not getting the result we worked for-now off to surgery for my broken collarbone."
Lotto-Soudal manager Marc Sergeant said: "Of course we are disappointed that we had such bad luck today. As a team we probably rode one of our best editions of Milan-San Remo.
"Until ten kilometres from the finish Jasper De Buyst, Jens Debusschere and André Greipel were still part of the first group. Jasper and André crashed on the descent of the Poggio.
"Jens Debusschere got held up because of that crash. We had already lost Jens Keukeleire just before the foot of the Poggio. He had already done a lot of work by that point, just like Bak, Maes and Sieberg.
"As a team we performed very well. Everyone was strong, but luck was not on our side.”
Greipel had already shown that he was in good shape this season, with two stage wins at the Tour Down Under in Australia in January.
On Monday afternoon, Lotto-Soudal issued an update on Greipel's surgery, which reportedly required a plate and 10 screws to fix his collarbone in place, undertaken by Dr Toon Claes in Herentals
Greipel said after the surgery: "Doctor Claes said it was a difficult, but successful operation. The collarbone was broken into different pieces. I already could go home this morning.
"The upcoming week I need to leave the bike aside and afterwards, depending on the amount of pain I have, I can start riding on the rollers. The next weeks I can’t ride any races, so I try to be patient and not to rush anything.”
“I immediately felt my collarbone was broken. Scans in the hospital of Nice Saturday night confirmed that. As a rider you always hope for a miracle, so you can start in the Classics, but that hope disappeared quickly. The next weeks will be all about rest and rehabilitation and I will come and cheer for the team in one of the races. Unfortunately this is also part of a cyclist’s life."
The team reports that both De Buyst and Keukeleire suffered abrasions, but with no other significant injuries.
Greipel was not the only notable sprinter to have crashed out of the 2018 edition of Milan-San Remo. British Dimension Data rider Mark Cavendish hit a bollard on the approach to the Poggio and was sent flying through the air, landing heavily on the road.
Cavendish's team reported that he suffered a possible ankle injury, abrasions and a fractured rib, separate to the one he also fractured in Tirreno-Adriatico.
Nibali's attack on the Poggio ultimately netted him the Milan-San Remo victory, with Caleb Ewan (Mitchelton-Scott) leading the peloton home for second place.
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