Italy's highest criminal court has overturned the acquittal of Amanda Knox and her ex-boyfriend for the murder of British student Meredith Kercher, and ordered a retrial.
Knox and Italian Raffaele Sollecito, who were originally sentenced to 26 and 25 years in prison for killing and sexually assaulting Miss Kercher in 2007, were acquitted on appeal in 2011 after four years in prison.
Reacting to the Supreme Court's decision, Knox said it was "painful" to have the acquittal overturned "when the prosecution's theory of my involvement in Meredith's murder has been repeatedly revealed to be completely unfounded and unfair".
Mr Sollecito's girlfriend Maria has reportedly told an Italian television station that he will be moving with her to Lugano in Switzerland and that both Amanda and Raffaele are "devastated" at the news. She added that Amanda has told her there is "no way" she will be coming to Italy.
Ms Kercher, 21, was found half-naked with her throat slashed in a pool of blood in her bedroom in the house that she shared with Knox in Perugia in November 2007.
The sister of the murdered Briton, Stephanie Kercher, told Sky News her family welcomed the ruling by the Italian court.
Speaking from Coulsdon in Surrey, the elder sibling said there were "still questions that are unanswered and we are all looking to find out the truth".
"Rudy Guede was convicted along with others, so we need to find out who those other people are, but as a family we know there is still a long way to go.
"We welcome the decision that a retrial has been ordered and are pleased it is a step forward to finding an answer to some of those questions," she added.
Knox returned home to Seattle immediately after her release. It is possible that she will be tried in absentia in the new hearing, which will take place in Florence, because the United States does not normally extradite its citizens to face legal action.
Knox's lawyer Carlo Dalla Vedova said the 25-year-old student was upset but "willing to fight" and had not yet decided whether she would turn up for the trial in person or not.
A date for the retrial has not yet been set, but it is thought it could be as early as the summer. It is understood that all the DNA evidence will be reviewed.
A third person, Ivory Coast-born drifter Rudy Guede, who like the other two has always denied the murder, is the only person still in jail for the crime.
After choosing to undergo a separate, fast-track trial in 2008, he was found guilty of sexual assault and murder and sentenced to 30 years in prison. This was reduced to 16 years on appeal.
The Kercher family insists that 47 knife wounds on Meredith and the apparent use of two different knives in the attack meant that more than one killer was involved, leaving the second murderer still at large.
Initial handling of the long-running case has been sharply criticised by independent forensic experts.
In her statement following the Supreme Court's decision, Knox said: "I believe that any questions as to my innocence must be examined by an objective investigation and a capable prosecution.
"The prosecution responsible for the many discrepancies in their work must be made to answer for them, for Raffaele's sake, my sake, and most especially for the sake of Meredith's family. Our hearts go out to them.
"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."
Knox had been scheduled to speak about the trial for the first time on American television in April, when her book about the case, called Waiting To Be Heard, is due to be released.
Sollecito, who turned 29 on Tuesday, is now living with his family near Bari in southern Italy.
Before the decision was known, Giulia Bongiorno, the lawyer representing Sollecito said she was convinced the court would not over-rule the acquittal.
"We are hopeful. We know Raffaele Sollecito is absolutely innocent and we expect that it ends here. Even if it doesn't end here we just need to follow the precis, but I am convinced this case will end here," she said before entering the court.