As an undergraduate at Cambridge University Lettsom befriended the author William Makepeace Thackeray and was the (or an) editor of The Snob in which some of Thackerays earliest work appeared; Lettsom has been identified as the character Tapeworm in Thackerays novel Vanity Fair, a diplomat who fancies himself as a ladies man.  Lettsom was well acquainted with the cartoonist George Cruikshank, illustrator of the early works of Charles Dickens.  Lettsom was a contributor to various literary periodicals under the pseudonym Dr. Bulgardo'.