I wonder ... when you save, and are prompted to overwrite the file, is it set up to be a Quark 6, and not a Quark 5, file?
Because if memory serves, when you are working on a Quark 5 doc in Quark 6, each time you save, it will prompt you to overwrite the existing file IF you're keeping the file in Quark 5 format.
If that fails, quit Quark, make a duplicate of the file in the Finder, and try working with the dupe for a bit and see if the behavior persists.