Former Giro d'Italia winner Danilo Di Luca tested positive for EPO in a surprise check at his home before this year's race, organizers said.
If confirmed in a backup "B'' sample, Di Luca risks a lifetime ban since this is his third offence.
"I wasn't expecting this. It was a surprise for me. I'm disappointed," Di Luca said upon leaving his team's hotel in northern Italy. "I'll ask for the backup analysis then we can talk again."
Armstrong appeared surprised, too.
"Knowing I have 0 cred on the doping issue - I still can't help but think, 'really Di Luca? Are you that ... stupid??" Armstrong tweeted, inserting a vulgarity between "that" and "stupid."
It's the second doping case from this year's Giro, after French rider Sylvain Georges tested positive for the banned stimulant Heptaminol in a urine sample after the seventh stage. The 28-year-old AG2R La Mondiale rider was immediately withdrawn from the race.
The UCI provisionally suspended Di Luca pending a hearing with the Italian cycling federation and the Vini Fantini-Selle Italia squad fired the 37-year-old Italian rider.
"Danilo has betrayed cycling once again," Giro race director Mauro Vegni said. "But I'm happy it wasn't a young rider. Danilo belongs to a generation that has navigated through the doping system."
After being stripped of his seven Tour de France titles, Armstrong confessed to doping in a TV interview in January with Oprah Winfrey. And while many of Armstrong's former teammates have also come forward to say they doped, some of the riders who supported the Texan during his career continue to race.
Longtime Armstrong lieutenant Yaroslav Popovych, a Ukrainian rider with the RadioShack-Leopard team, sits 139th overall in the Giro.
The test on Di Luca was carried out April 29, five days before the Giro started, and the result drew a harsh rebuke from Vini Fantini team director Luca Scinto.
"Di Luca is an idiot. I never wanted him," Scinto said. "Di Luca is sick. He needs to be helped."
Seemingly headed for retirement just a few months ago, Di Luca signed with Vini Fantini on April 26. Scinto and others were against hiring him but sponsors eventually prevailed.
"The sponsors chose him and now they've got to take responsibility," Scinto added.
The team is considering suing Di Luca for damaging its image.
The race ends Sunday and Di Luca departs in 26th place overall, 33 minutes, 33 seconds behind overall leader Vincenzo Nibali.
The announcement came a day after the 28-year-old Nibali extended his lead by dominating a mountain time trial, garnering headlines up and down Italy as the new face of the sport.
Italian cycling federation president Renato Di Rocco called for "the most severe punishment."
"We can put out there all the prevention instruments we want — both in terms of informing and testing — but we are weaponless when faced with stupidity," Di Rocco said. "(Di Luca) has especially betrayed the new generation of cyclists that are restoring the credibility and image of Italian cycling."
In 2009, Di Luca was given a two-year ban after testing positive during the Giro for CERA, an advanced form of the blood booster EPO. That ban was subsequently reduced by nine months after he collaborated with Italian anti-doping authorities.
And after winning the 2007 Giro, Di Luca was banned for three months later in the year for frequent visits to Carlo Santuccione, a physician at the centre of a four-year doping investigation titled Oil for Drugs.
Di Luca was stripped of his second-place finish and two stage wins in the 2009 Giro, which was won by Denis Menchov, a Russian rider who was never banned for doping but was often linked to banned drug cases.
Armstrong raced the Giro for the only time in 2009 but did not contend for the title.
Di Luca fared well in several stages of this year's Giro, finishing third in the seventh leg, seventh in Stage 9, sixth in Stage 11 and 10th in Thursday's uphill time trial.
"He wrote me a text message saying, 'I don't know what to say. I'm sorry,'" Giro director Michele Acquarone said. "If someone looks you in the eye and asks for your support and then betrays you, then it means he has a serious problem — in this case a strong addiction."
The Giro's 19th stage on Friday was cancelled due to snow.Suggest a correction