When purchasing a used pistol, is there any issue (other than possible re-sale value) if the serial number on the frame is different from the serial number on the slide?

Depends on the gun. Most semiautos have un-numbered slides. What is it that you have?

The frame is the receiver in ATF speak, so that serial number is the only one that matters to them. Think how many mix master milsurp rifles are out there and it's no big deal.

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Release the Kraken

The gun is a Sig P230.