What OS and AMD driver are you using? I would try using an older/newer driver depending on the driver you are using at the moment.
If you can provide a picture of screenshot of what you are describing, that would be useful.
Thanks for your reply AMDMatt. I doubted if it was a software issue as I have 3 identical Z800s I've moved the card across and 2 identical R9 280x cards. The problem only occurred on one of the 3 video cards and appeared across all three platforms...but I post the information below because you are right, it should be posted with any question.
Be that as it may, I did notice that the square of larger pixels moved around between machines so I thought...maybe its the old slightly tarnished gold connector thing on the PCIe buss. So I reverted to my 1980s technology, got out my pencil eraser and made the gold contacts shine. Strangely it worked. So the square went away.