Aru was looking forward to challenging defending champion Vincenzo Nibali (Bahrain-Merida) and Nairo Quintana (Movistar) for the Giro title.
His Astana team said he is suffering from "prepatellar bursitis", an irritation which causes pain when he pedals. An injury brought on by a crash while training in Spain.
After examination in Milan, doctors recommended 10 days of complete rest, something he could ill afford to take with the Giro d'Italia less than a month away.
The diagnosis will be crushing for Aru not only because he will miss the event's 100th edition but the race start, which begins on his home island, Sardinia.
“I’m so sorry and disappointed for what happened," he said. "I was dreaming of the Giro Start from Sardinia and we were preparing for the Giro for months.
"Unfortunately, the accident occurred and doesn’t allow me to be at the start in sufficient condition. With great regret, we are forced to give up."
At this stage of his career, the somewhat mercurial Italian remains a rider with potential despite a result sheet most professionals in his age cohort would kill for.
He has already won a Vuelta a España (2015) and finished on the podium at the Giro d'Italia twice but real consistency eludes him.
This year he has raced at the Tour of Oman and Abu Dhabi Tour for a podium place and a top-ten result. Strade Bianche produced an outside the top-30 result and then he abandoned Tirreno-Adriatico after Stage 4 with a bout of bronchitis.
He is one of the most entertaining and dangerous Grand Tour riders out there but if Aru does have a consistency right now, it's inconsistency. Though his prodigious talent and often dynamic riding suggest there is a lot more to come.
The team said his race calendar "will be evaluated after his complete recovery from this injury" which could mean another tilt at the Tour de France.
His expressive nature would not only add even more depth to an already stacked event, it would likely shake up the race at key points.
The 26-year-old has raced the Tour once (2016), finishing 13th overall and not quite meeting the perhaps unfairly high expectations placed on him prior to the 2 July Mont Saint-Michel start in Normandy. It was a result which dented his confidence.
"I'm still struggling to get over it, I'm not going to deny it," Aru told La Gazzetta dello Sport last year. "I've thought about it a lot and I realised I made a lot of mistakes. I didn't know how to handle the flat stages and the windy days were a real eye opener for me."
Learning from that, team management had decided to spare him the Tour in 2017 and instead focus on the Giro and Vuelta and leaving a return to France for another year.
Hopefully, he and Astana will reconsider and the Giro's loss will be the Tour's gain.