there can be
on some very intensive programs... that are written specifically for x64 (the latest photoshop is an example) there are improvements w/ x64 over x32
but you need 64-bit drivers and hardware.
its installer may be 16-bit
or... some programs are just written 'poorly' (for a lack of a better term) and just can't run on that architecture.
I know people have issues installing the Focus Magic Photoshop CS4 plugin on x64 machines