A mother has been charged with the murder of her daughter, who went missing from their NSW Hunter Valley family home 15 years ago.

Leonie Astra Hutchinson was 16 months old when she was last seen in Scone in 2001 but not officially reported missing until January 2004.

Detective Chief Inspector Tim Seymour said police had no doubt the toddler was dead and they had conducted searches for her remains in several places.

The child's mother, Kate Hutchinson, 43, was arrested at her home in Evans Head on the state's far north coast on Wednesday morning and has been charged with murder.

Kate Hutchinson was arrested at her home in Evans Head. ( Supplied: NSW Police )

A coronial inquest into the matter in 2013 heard Hutchinson was involved in witchcraft and police subsequently searched the family home at Scone.

Investigators believe the child was last seen alive at the property sometime around January 2001.

Detective Inspector Seymour said the investigation had lasted more than a decade.

"The arrest was the culmination of the investigative process from the evidence that we've gathered from members of the public and other means, an inquest was held and that's what lead us to this point," he said.

"It has showcased the dedication and resilience of investigators and the police attached to Strike Force Kununa have shown great dedication bring this to the arrest phase.

"We're still searching for the remains of the toddler and I would appeal to anybody at this point who has any information to contact Crimestoppers."

'Different hypotheses' about Leonie's disappearance

The detective said he could not comment on whether there was a specific recent discovery that led police to Hutchnson's arrest.

He said that the matter was an ongoing mystery that people had had different hypotheses about what had happened over the years.

"It's part of what we do, it's our business, not to let go and to continue to investigate these matters."

Strike Force Kanuna was formed to investigate Leonie's disappearance, and comprises detectives from Hunter Valley Local Area Command, assisted by State Crime Command's Homicide Squad.

Hutchinson was refused bail at Lismore Local Court and is due to reappear in the same court on March 22.

Darrin Penfold, who lived next door to the house where Hutchinson lived at the time of her daughter's disappearance, said it was time there was some closure on the case.

"It's been going on for so long, and now the little girl who can finally be at rest," Mr Penfold said.

"It's just sad, mate, terrible. The police were here for about a week and a half, digging underneath the house and taking dirt from under the house, trying to find the little girl's remains but they didn't prevail with that."