Knox, 23, and her former Italian boyfriend Raffaele Sollecito were jailed in 2009 for 26 and 25 years respectively for the murder of Meredith Kercher but are appealing. Ivorian Rudy Guede was also convicted of the murder.
Kercher, a 21-year-old English student, was found half naked in November 2007 with her throat cut in the house she shared with Knox in the university city of Perugia.
The judges said the murder was the result of a frenzied sex game that spiralled out of control in a case that has attracted huge media attention, boosted by the Seattle student's good looks.
Independent forensic experts appointed by an appeal court at the request of the pair's defence said in a report lodged on Wednesday that DNA evidence used in the trial was unreliable and numerous errors had been made by police scientists.
Significantly, they said no evidence supported the original police conclusion that Kercher's blood was found on a knife which they identified as the murder weapon and which had been handled by Knox.
The experts, Carla Vecchiotti and Stefano Conti, confirmed police conclusions that Knox's DNA was found on the handle of the knife but said material on the blade was from starch.
The experts also said there was no DNA evidence on a clip from Kercher's bra which police said was traceable to Sollecito, 27. The report was obtained by journalists at the court.
In a scathing indictment of the methods of the Italian police, the experts said tests on the blade of the knife "as obtained appear unreliable because not supported by scientifically valid analytical procedures."
They added: "International procedures for inspection and protocols for collection and testing of the evidence were not followed.
"We cannot exclude that the result obtained from the blade of the knife could derive from contamination in some phase of handling or analytical processing of the samples."
The experts reached similar conclusions about the bra clip, saying the tests taken had been wrongly interpreted and did not follow international protocols. They also could have been contaminated, the experts said.
Knox's Italian lawyer Luciano Ghirga told Reuters the report "is a big blow to the scientific evidence. We are happy with the result even if it has come late."
He said the forensic report would be considered by the next hearing of the appeal trial in July and he would show the findings to Knox in jail Thursday.
Sollecito, Knox and her family and friends have always denied the pair committed the murder.
Earlier this week Knox clashed in court during the appeal hearing with 24-year-old Guede, who is serving 16 years for Kercher's murder but is not part of the appeal.
She told the court she was "shocked and anguished" by evidence from Guede that she and Sollecito killed Kercher.
The body of the English student was found locked in her blood-spattered bedroom in the house she shared with Knox and two other students. She had a deep stab wound to the throat.
Prosecutors accused Knox of persuading Guede and Sollecito to take part in an extreme sex game that turned violent. They said Knox was furious at Kercher because she criticised her for lack of cleanliness and for allegedly being promiscuous.