In principle, the smallest change possible is a single nucleotide substitution: the change of one base of DNA into another. Or, similarly, the insertion or deletion of a single base.
At the genetic level this is true; but natural selection can only act on phenotypes (and I think that is what the OP was talking about). Point mutations can have quite large effects, or almost no effect; larger changes can also have large effects, or almost no effect.
Look at the plants and animals around you, InGodITrust, and consider the range of individual variation you can see; consider the smallest difference that might be possible between two such individuals - evolution can work with that; whether it's fur a millimetre longer, or a slightly enlarged leg muscle, or a tiny difference in the light wavelengths that are best percieved.
(Although, as should be noted, a decent portion of individual variation is environmentally influenced)
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