Isabelle Dinoire, 49, succumbed to two types of cancer earlier this summer after a decade taking powerful immunosuppressant drugs.
The drugs were designed to prevent her body rejecting new tissues, but they always threatened to make Ms Dinoire seriously ill.
Miss Dinoire, from Valenciennes, northern France, captured the imagination of the world in November 2005 when she was given a new nose, mouth and chin at the nearby Amiens Hospital.
She was rushed to hospital after her pet dog apparently ripped off the vital features, but she had no memory of what happened.
After taking sleeping pills, all the divorced mother of two could remember was waking up with blood on the floor of her flat.
It took a team of med led by Professor Bernard Duvauchelle, an oral and maxillofacial surgeon, 15 hours to perform the medical breakthrough.
A triangle of face tissue from a brain-dead woman's nose and mouth were grafted onto Miss Dinoire.
Three years on, Miss Dinoire admitted that she remained uncertain as to whose face she looked at in the mirror every day.
Referring to the dead donor, she said in 2008: ‘It's not hers, it's not mine, it's somebody else's.
‘Before the operation, I expected my new face would look like me but it turned out after the operation that it was half me and half her.’
A report in the news outlet’s health pages today reads: ‘Isabelle Dinoire died this summer. She was the first patient in the world to benefit from a face transplant in 2005.’