DNA ruled out a suspect the FBI believed was D.B. Cooper, the man who hijacked a jetliner in 1971 before jumping from the rear of the plane with $200,000 in cash.
The FBI has said DNA didn't provide a match to material found on the necktie the hijacker left behind on the plane.
That the evidence failed to tie the suspect to the hijacker is a major blow for the FBI, which has been tracking hundreds of leads in the 40-year-old case.
But Special Agent Fred Gutt has cautioned that the recent test doesn't necessarily rule out the dead suspect because there are three different DNA samples on the tie and it's unclear where the hijacker got it.
"There are some questions about the tie itself: Was it a used tie, a borrowed tie?" Gutt told the Seattle Times.
The FBI recently announced a promising new lead pointing to a man who died about 10 years ago in the Pacific Northwest as D.B. Cooper.
Marla Cooper, who claimed to be the hijacker's niece, recently came forward and said she had a role in renewing the FBI's probe into the cold case.
Marla Cooper told ABC News she is sure that her uncle Lynn Doyle Cooper was the man who pulled off the notorious 1971 hijacking and parachuted from the plane with the money.
Marla Cooper said she is certain after clarifying childhood memories about the incident and through recent conversations with her parents. She even recalled being 8 years old and hearing her two uncles making suspicious plans at her grandmother's Oregon home, near where D.B. Cooper jumped.
"My two uncles, who I only saw at holiday time, were planning something very mischievous," she told ABC News. "I was watching them using some very expensive walkie-talkies that they had purchased. They left to supposedly go turkey hunting, and Thanksgiving morning I was waiting for them to return."
About a day later, Northwest Orient Flight 305 was hijacked, and her uncle L.D. Cooper came home and said he was in a car accident.
"I heard my uncle say we did it, our money problems are over, we hijacked an airplane," she added.
Marla had given the FBI a guitar strap and a Christmas photograph of her uncle pictured with the same strap.