Having recently setup DFS-R and DFS name spaces we found that our users were reporting that a security warning was popping up every time they opened any file from our DFS shares (example above).
The warning in Word 2010 was
The file originated from an Internet location and might be unsafe. Click for more details.
The silly thing about it is its not an Internet location its an Intranet one.
As it turns out because I was using a FQDN to connect to our DFS shares Windows was picking up the files as coming from the Internet.
The simple solution to this problem is to manually define your FQDN as a Intranet Zone in Internet Explorer (screen shots below show how to do this via GPO).