Well, I can't write up a big description right now, but they're definitely completely different sorts of things.
The basic way I'd think of it is that LISP lets you do clever things by keeping the core design of the structures inside of the compiler/interpreter as simple/primitive as possible.
Smalltalk lets you do clever things by having the run time system "take care of the hard stuff for you."
...Although maybe this description is overly simplistic.