I recall hearing about one *very* critical security patch for NT4 that broke some installs of Exchange. I also seem to recall hearing about a similar situation on W2K.

There's a server I have the misfortune to have to maintain in part that CAN'T have one particular security patch installed (or service pack, I don't know the details offhand as I didn't set it up), or the third-party IIS-dependant library catalog software (supposedly THE standard package for this purpose) breaks- horribly. Fortunately, this machine *does* have a decent third-party firewall installed, otherwise it would have been thoroughly infected with one or more of the RPC-exploit worms out there.

I've even seen service packs cause odd things to happen on my own workstation boxen occasionally.