How Armstrong, who is accused of but has consistently denied systematic doping, managed to evade detection will also dog the sport of cycling, which has sought to improve its image after a series of damaging drug scandals.
Potentially central to the implications of the US Anti-Doping Agency (USADA) report, published on Wednesday, could be a section in the 202-page document entitled "Perjury and Other Fraudulent Conduct to Obstruct Legal or Judicial Processes."
In it, the organisation documents what it says were Armstrong's "false statements under oath... and subject to penalties of perjury" in legal proceedings in the United States and France concerning accusations of doping violations.
They include statements made denying any links to Michele Ferrari, the former team doctor of the Gewiss-Ballan team, who has been implicated in the possession, trafficking and administration of banned substances and assisting doping.
Armstrong denied being encouraged by Ferrari to take performance-enhancing drugs, using banned substances in his career or seeing team-mates do so.
The USADA, which said doping orchestrated by Armstrong at his US Postal Service team was "more extensive than any previously revealed in professional sports history", said the rider's testimony was "materially false and misleading when made."
The body also accused the Texan of trying to "procure false affidavits from potential witnesses" in a US Department of Justice and USADA case against him in August 2010 to say there was no systematic doping in the team.
"Consequently, Mr Armstrong's efforts constituted an attempt to subvert the judicial system and procure false testimony," the report added.
The report also accused Armstrong of witness intimidation to prevent team-mates from testifying.
Whether further action is taken over what the report said was "the evidence of efforts by Armstrong and his entourage to cover up rule violations, suppress the truth, obstruct or subvert the legal process and thereby encourage doping" is unclear.
But there is little doubt that the long-running affair has cast a pall over cycling.
Michael McCann, a legal expert in sports law, told AFP on Thursday that criminal prosecution against Armstrong would be unlikely but "not impossible."
"It would be unusual, improbable but not impossible" to reopen the investigation," said McCann, the director of the Sports Law Institute at the Vermont Law School.
"Usually there's no second grand jury, but there's no rule against that. It is possible but it would be an unusual development."
Armstrong has only tested positive once -- for a corticosteroid at the Tour de France in 1999 -- but cycling's world governing body, the International Cycling Union (UCI), did not sanction him.
Now, amid claims of his close links to Ferrari, alleged use of the banned blood booster erythropoietin (EPO), testosterone and blood transfusions, the UCI will surely have to respond as to the rigour of its testing programmes.
Also unclear are what the repercussions for cycling will be, just as it seeks to clean up the sport and move on from repeated doping scandals, particularly in its most celebrated race, the Tour de France.
The USADA report could not have come at a worse time for Tour organisers, as they prepare to unveil the route for the 100th edition and broaden its appeal beyond its traditional heartland of France and continental Europe.
If the allegations and ban against Armstrong are upheld, there is a precedent for replacing Armstrong's name at the top of the Tour de France classification.
Floyd Landis, Armstrong's former team-mate, was stripped of his 2006 title and later admitted doping. Spain's Alberto Contador also lost his 2010 win to Andy Schleck after a doping violation.
But with the majority of riders who made the podium from 1999 to 2005 having subsequently been implicated in doping cases, finding a winner could be difficult -- if not impossible.
Armstrong's future in triathlon, in which he has become a prominent competitor, could also be in doubt, because the sport appears split on whether he should be allowed to take part.
"I don't want to see the sport as a place where dopers come when they can't compete in anything else," Paulo Sousa, a veteran triathlete and coach, told The New York Times.
Armstrong's sponsors, including sportswear giant Nike, have so far not withdrawn their support but he could yet face a financial hit if he has to repay millions of euros in prize money for his Tour victories and win bonuses.