I have a program working in the Android Emulator. Every now and again I have been creating a signed .apk and exporting it to my HTC Desire to test. It has all been fine.
Apparently this can also be caused by renaming the APK prior to installing it. I wanted to reduce the amount of typing users had to do to get the app from our web site by shortening the file name. After that, they were unable to install it.
Once I reverted to the original file name used when creating and signing the package I was able to update the installed app.