The development of Hannibal Lecter into one of the great fictional villains sets this book apart from Red Dragon, where Lecter first appears. Of the other characters common to both novels, Jack Crawford, head of the Behavior Science division which tracks serial killers, has a considerably more important role in The Silence of the Lambs, both as Starling's mentor and as a husband dealing with the death of his wife.

Like Red Dragon, this novel shows Harris moving in a decidedly more literary direction, with epigrams, literary references, and archetypal characters who achieve both personal and symbolic significance. Given this movement in his work, the competent writer of thrillers who produced Black Sunday (1975) is long gone, replaced by a writer of great sensitivity and style who just happens to know how to weave a great thriller.