The two were initially convicted in 2009 for the frenzied murder of Meredith Kercher in Perugia in what prosecutors say was a sex game gone wrong, then absolved on appeal in 2011 after nearly four years in prison.
But that ruling was reversed in 2012 over "contradictions and incoherencies", particularly over crucial DNA evidence that had been challenged by the defence, meaning the case returns to the appeal stage.
The case will be heard in a court in Florence.
Knox is now in the United States and is highly unlikely to return to Italy voluntarily, although there is a very remote chance that she could be extradited and imprisoned if she is convicted.
The only person behind bars for the murder is Rudy Guede, a local drifter born in Ivory Coast who is serving a 16-year prison sentence after being tried separately and convicted of murder and sexual assault.
Based on the physical evidence, prosecutors say the murder could not have been carried out by one person.
Kercher was found half-naked in a pool of blood on November 1, 2007 in the house she shared with Knox.