Armstrong said in the interview that he stopped doping following his 2005 Tour de France victory and did not use banned substances when he placed third in 2009 and entered the tour again in 2010.
Investigators familiar with Armstrong's case, however, told ABC News today that Armstrong did not come completely clean to Winfrey, and that they believed he doped in 2009.
They said that Armstrong's blood values at the 2009 race showed clear blood manipulation consistent with two transfusions. Armstrong's red blood cell count suddenly went up at these points, even though the number of baby red blood cells did not.
Investigators said that was proof that he received a transfusion of mature red blood cells.
If Armstrong lied about the 2009 race, it could be to protect himself criminally, investigators said.
Federal authorities looking to prosecute criminal cases will look back at the "last overt act" in which the crime was committed, they explained. If Armstrong doped in 2005 but not 2009, the statute of limitations may have expired on potential criminal activity.
The sources noted that there is no evidence right now that a criminal investigation will be reopened. Armstrong is facing at least three civil suits.
Armstrong passed more than 500 drug tests during his career. In some cases, however, he was found to have used substances, including EPO, years after he retired when new tests could find previously untraceable drugs.
In October, the report released by the U.S. Anti-Doping Agency featured 11 of Armstrong's former teammates describing how they and Armstrong received drugs with the knowledge of their coaches and team physicians.
The U.S. Postal Service Cycling Team "ran the most sophisticated, professionalized and successful doping program that sport has ever seen," USADA said in its report.
Following the report, Armstrong was stripped of his seven Tour de France titles and lost his $75 million sponsorship deal with Nike, among others. This week, the International Olympic Committee stripped Armstrong of a 2000 Olympic bronze medal.
"It was a mythic perfect story and it wasn't true," Armstrong said of his fairytale story of overcoming testicular cancer to become one of the most celebrated cyclists in history.
READ MORE: Did Doping Cause Armstrong's Cancer?
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ABC News' Russell Goldman contributed to this report.