A tiny sample of female DNA was found under the fingernail of murdered schoolgirl Raonaid Murray.
The microscopic discovery does not match any of Raonaid's friends or family, who had been with her in the days leading up to her death.
It was found following scientific advances in DNA profiling.
In recent weeks, detectives have taken DNA samples from more than 50 women to eliminate them from further inquiries.
The development has supported the theory that Raonaid (17) was killed by a woman.
The garda's cold case unit has made the unsolved murder the focus of an active review.
It identified shortcomings in the original investigation and pinpointed new leads for detectives to follow, including the location of a young woman seen close to the murder scene.
She is described as having been aged 16 to 23, with shoulder-length hair, and was seen walking away from the scene around 15 minutes after Raonaid's body was found. She has never come forward.
Raonaid, from Silchester Park, Glenageary, was stabbed to death in a lane close to her home after leaving Scott's pub in Dun Laoghaire on September 4, 1999.
She was stabbed up to 30 times. Her clothing was not penetrated by some of the jabs, suggesting her attacker may have been a female.
Raonaid survived the initial attack and managed to make it to within 50 yards of her home before succumbing to her injuries.
The type of weapon used in the killing is thought to have been a kitchen knife. It was never found.
Gardai believe her murder was not the work of a random killer.
There was no evidence of a sexual assault. A shoulder bag and plastic carrier bag the victim had been carrying were untouched.
More than 100 officers were assigned to the inquiry at the height of the investigation, but the killer was not identified.
Raonaid's parents Jim and Deirdre Murray have continued to appeal for witnesses to their daughter's murder, and, in September, made a renewed appeal to help to solve the killing.