Betty Brown, 56, was last seen on May 28, 2010 travelling on the No 3 bus in Nicolson Street in her home city of Edinburgh.
It is thought she then travelled on the X95 bus from Edinburgh to Gretna or Cumbria.
Ms Brown's body was discovered in woods near a disused quarry in Longtown, Cumbria, on January 18, 2011. Detective Inspector Doug Marshall said: "It's a twofold appeal really. It is for anybody who might have been in the area at the time at the end of May in 2010 who hasn't been spoken to by the police and didn't see the media coverage at the time.
"The second aspect is that it is now, two years on; loyalties change. People may have known something at the time they didn't feel able to come and tell the police, and we are appealing to them to come forward now with any information they may have.
"The important part of it is we've never been able to go to Betty Brown's family and tell them exactly what's happened to her, and obviously that's been a cause for concern for us right from the start from when we started treating the discovery of the body as suspicious.
"There may be somebody out there who has been told something about what happened to Betty in those woods and, if somebody does know something, for the sake of this family we ask them to take the step of coming forward to the police."
On the day she was last seen, Ms Brown was carrying two large black Aldi bags which were discovered near where her body was found.
Money was taken out of her account at the Royal Bank of Scotland cash machine in Nicolson Street the same day. Police believe Ms Brown, of Gorgie Road, made the withdrawal.
Cumbria Constabulary said Ms Brown had family in the Gretna area and when visiting them she would get the X95 bus from Edinburgh to Longtown.