The body of Lindsay Rimer, 13, was found in the Rochdale Canal five months after she disappeared in Hebden Bridge, West Yorkshire, in November 1994.
Her killer has never been found and West Yorkshire Police are treating the death as murder.
The force said a new DNA profile had been identified, which it hoped would lead them to identify the killer.
Speaking on the anniversary of the discovery of her body, Det Supt Simon Atkinson said: "Our Canadian colleagues are doing some ground-breaking forensic work, so we've sent some of the forensic exhibits over to them.
"They have been able to develop a DNA profile which we are really interested in developing further."
He added: "It's a leap forward we haven't had in the past 21 years, so I'm really excited about this development."
Lindsay left her home in Cambridge Street at about 22:00 and visited the Trades Club in Home Street.
The last known sighting of her was caught on CCTV 20 minutes later as she bought cornflakes at a shop in Crown Street.
Her body, which had been weighted down with a stone, was recovered about a mile upstream from the town centre.
Juliet Rimer, her younger sister, said: "A piece of everyone's soul is missing and I often wonder how our lives would have been, if we were not a broken family.
"The advice Lindsay would have given me, the fights we might have had, and the things we may have shared.
"Getting the answers wouldn't change the hurt, but it would help bring closure to us all."
New forensic leads are being investigated in connection with the death of a schoolgirl 21 years ago.