In a statement, the 34-year-old American, said: "The latest story, which alleges an admission of using performance-enhancing drugs in a hospital in 1996, is today as absurd and untrue as when it was first circulated years ago. It never happened."
He described the allegations in the newspaper as "stale, unfounded and untrue."
Armstrong, who retired after his record seventh consecutive Tour victory last July, has always denied taking banned substances.
Le Monde reported that according to testimonies gathered from Oct. 2005 to Jan. 2006 by a court in Dallas, Armstrong "told an Indiana University Hospital doctor on Oct. 28, 1996 he had taken performance-enhancing drugs.
"The doctor questioned him on a possible use of doping products after his brain surgery in order to prescribe his post-surgery treatment," the paper said.
"In front of (former team mate) Frankie Andreu and his wife, who have testified under oath in Dallas, Armstrong said he had taken 'EPO, testosterone, growth hormones and cortisone'."
"My doctor, one of the premier cancer specialists in the country, also testified no such statement was made by me to him and a statement made to another would have to appear in the records. It's not there because it never happened."
Armstrong went to the Dallas court to refer a dispute with his insurance company to arbitration. SCA had refused to pay the Texan a five-million-dollar bonus following his victory in the Tour de France in 2004.
"The hospital allegation was made against me during a trial before three highly astute and respected arbitrators by an insurance company as its basis for not paying a $5 million bonus (and to recover $4.5million paid for 2002 and 2003 bonuses) for winning the 2004 Tour de France," Armstrong said.
"Not only did I win this trial, but the company was ordered to pay the $5 million plus an additional $2.5 million in penalty.
"The event reported in France never happened and the evidence presented to the panel proved it never happened."
Armstrong added that he had instituted proceedings to determine who had released documents and testimony from the case to the media.
The American had revealed in October 1996 he had undergone surgery to cure testicular cancer with metastasis in his brain and lung. He returned to cycling in 1999 to record his first Tour victory.
In a separate matter, French sports daily L'Equipe reported last August that it had access to laboratory documents and six of Armstrong's urine samples collected on the 1999 Tour showed "indisputable" traces of the blood-boosting drug erythropoietin.
Lawyer Emile Vrijman, a former director of the Netherlands' national anti-doping agency, was appointed by the International Cycling Union last October to investigate the allegations.
Vrijman cleared Armstrong in May, saying the World Anti-Doping Agency (WADA) and the French national doping laboratory had effectively pronounced the rider guilty of a doping violation without sufficient basis.
WADA head Dick Pound rejected the Vrijman report as "bordering on the farcical" and Armstrong last weekend called for disciplinary action to be taken by the International Olympic Committee against Pound, an IOC member.
Armstrong concluded in Friday's statement: "During my professional cycling career, particularly during its last seven years, I have had to repeatedly address this issue, which I have willingly done.
"Further discussion by me serves no purpose other than to dignify accusations which have been repeatedly investigated and rejected by every body, tribunal and court to consider them.
"I will not further dignify them, although I have authorised my legal representatives to provide responsive documents when appropriate."
(Writing by Alison Wildey in London)