Sarah Benford, who will now be 16, went missing from Welford House children's home in Northampton on 6 April 2000.
Her family, who live in Kettering, has not seen her since.
On Friday, her family will join Detective Inspector Allan Law on television to ask Sarah to get in touch.
Police believe she may be sleeping rough in London.
Detective Inspector Law said: "I am appealing for Sarah to get in touch with me or her family to let us know she is safe and well.
"She is not in any trouble with the police or her family. We just want to know that she is OK.
"It is now more than two years since Sarah went missing and with her being just 16 years old, we are obviously extremely concerned for her welfare.
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Her family are really missing her
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Detective Inspector Allan Law
"We do not know where she is or what she is doing.
"This is the third Christmas Sarah will have been away from home.
"Her family are really missing her. We are appealing for her to come home for Christmas.
"If that is too much, all we are asking is that she makes one phone call home to say that she is safe and well.
"That would be the best Christmas present ever."
A £1,000 reward is being offered for any information leading to Sarah being found safe and well.
Website relaunch
Sarah's photo has been displayed on the side of 10 Ford lorries in the search for leads on her whereabouts.
Her face was also used to re-launch the Missing Children's Website in March this year and she was also featured on posters displayed at every Tesco store in the country.
Sarah or anyone with any information about her is asked to call Northamptonshire police on 01604 700700 or the National Missing Persons Helpline on 0500 700700.
Home For Christmas will be broadcast on Carlton TV across the London region on 20 December at 1430 GMT.