Are you sure you're not holding it upside down?
(Sorry, couldn't resist )
Is it an actual mouse, or a touch/trackpad? Even if not, there may be a "Mouse Orientation" (I think that's what it was called under Vista) that allows you to set the orientation, e.g. you could set it so that when moving the mouse in certain angle, the ponter will move upwards, or so on. Maybe that setting is messed up? Try lookng through your touchpad (if applicable) or mouse settings, it's been a while since I last used Vista but if need be I can get on a Vista machine and post the instructions, the procedure probably isn't a lot dfferent for XP. Again, it's not certain if you even have such option, but it's something you should look at.