Debbie Melo has been not been seen since June 20, 2000 with her husband Luiz reportedly being the last person to see her.
Her husband has never been ruled out as a suspect, with police now opening the case files for the first time as part of the 22nd anniversary.
Her family have all but given up hope that the mum from Taunton, Massachusetts, is alive and well - but they still want her found and back home.
At around 4pm on June 20, 2000, police say that Debbie's husband Luis told officers that after he drove her to a doctor's appointment the couple got into an argument on Route 18 in Weymouth.
Debbie Melo has been missing since June 20, 2000
Debbie's sister, Pattie White, told
CBS Boston's WBZ I-Team : "He just said that he dropped her off at the side of the road, they got into an argument, he let her out, he drove down to the end of the street turned around came back -- and that she was gone.
"That was his story. I asked him did you do something to her?' He said "No, no, no."
Debbie Melo's family have all but given up hope that she is alive and well but still want her found and back home over 20 years since she mysteriously vanished
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