Police say a handmade quilt depicting scenes from 14th Century Chester may have been stolen from the city's cathedral by a tramp.
The quilt was on show near the Cathedral Arch
The 6ft by 5ft quilt, worth about £13,000, was taken a week ago when the building was full of visitors.
It was made by American artist, B.J. Elvgren, who was inspired by a visit to the Chester Mystery Plays in 1992.
Cheshire Police said on Thursday they think the quilt was stolen to order, or taken by a vagrant to sleep under.
Chester Mystery Plays board bought the artwork and presented it to Chester Cathedral, where it has since been on permanent display.
The quilt was on show near the Cathedral Arch, where the original medieval plays were first performed.
The plays are medieval dramatisations of the Bible stories which portray God's intervention into human history.
Det Sgt Barry Brown, who is leading the investigation, said: "We have a number of lines of inquiry but we are keeping an open mind about the nature of the offender or offenders.
"We believe somebody must have seen it being taken but perhaps they thought the person removing it was a cleaner or had a legitimate reason for being there.
"It could easily have been stolen to order and then taken to a specialist antiques dealer to be sold on.
"At the other extreme we are also investigating whether a vagrant may be using it as a duvet."
The quilt is believed to have been taken sometime after 1400 BST on Wednesday 25 May.