US student Amanda Knox has said she will fight to clear her name after an Italian court overturned her acquittal for killing Briton Meredith Kercher.
Miss Knox and former Italian boyfriend Raffaele Sollecito face a new trial over the 2007 killing in Perugia.
They were freed on appeal in 2011 after four years in jail, but Italy's Supreme Court on Tuesday re-opened the case.
Miss Knox does not have to return from the US for the case, but if found guilty she could face extradition.
Mr Sollecito, 29, will not have to return to jail while the new appeals process goes ahead.
Both deny killing UK student Meredith Kercher, 21, who was found stabbed to death in the flat she shared with Miss Knox in Perugia in November 2007.
The case has drawn intense media interest in Italy, the UK and the US and put the Italian police and justice system under great scrutiny.
In a statement, Miss Knox, now a 25-year-old student in Seattle, described the court decision to reopen the case as "painful news".
"The prosecution's theory of my involvement in Meredith's murder has been repeatedly revealed to be completely unfounded and unfair," she said.
"No matter what happens, my family and I will face this continuing legal battle as we always have, confident in the truth and with our heads held high in the face of wrongful accusations and unreasonable adversity," she added.
Meredith Kercher's family has welcomed the decision.
"Whilst we are not happy about going back to court, and it will not bring her back, we have to make sure we have done all we can for her," Miss Kercher's older sister Stephanie said.
Kercher family lawyer Francesco Maresca said it was "an important day for the Italian legal system".
Miss Knox and Mr Sollecito were originally sentenced to 26 and 25 years in prison for murdering and sexually assaulting Meredith Kercher.
The Leeds University student was found with more than 40 knife wounds on her body, including a deep gash to the throat.
Prosecutors believe she died in a brutal sex game that went wrong.
Another man - Rudy Guede from Ivory Coast - was convicted in a separate trial and sentenced to 16 years for the killing.
In 2011 Miss Knox and Mr Sollecito were acquitted on appeal, largely on the grounds that DNA evidence was flawed.
But that decision has now been overturned by the Supreme Court after prosecutors argued that it was "contradictory and illogical".
The court has not yet given a full explanation for its ruling on the appeal, but will announce its reasons within 90 days.
The new trial will be held in Florence rather than Perugia, where the original trial and appeal took place, although the date has not yet been set.
After her release in 2011, Miss Knox returned to the US.
Both she and Mr Sollecito - now a student in Verona - have written books about the case.
Mr Sollecito's was published last year.
Miss Knox's book - titled Waiting to be Heard - is due out on 30 April.