In Thomas Harris' novel The Silence of the Lambs, the main them is relatively subjective. Given that the novel does not have an overlying theme, one can simply interpret what the message of the story is for themselves.
One could easily define any of the following as the main theme of the novel: good verses evil, the search for peace, judging a book by its cover.
For the theme of good verses evil, one only needs to examine the central action of the novel. The FBI is searching for a serial killer and Clarice Starling is assigned to the case. She must come to realize what is good and what is evil in the case, her life, and a key informant, Dr. Hannibal Lecter.
For the theme of one's search for peace, one must examine Starling's character. Readers find out about her past and how she remembers hearing lambs scream when slaughtered. Dr. Lecter brings this up. The screaming of the lambs comes forward into her present. NO longer are the lambs themselves screaming, but her ability to solve the case becomes her screaming lamb. The lambs will only become silent if Starling can solve the serial killer case.
The last theme, the problems associated with judging a book by its cover is relevant with many of the characters of the novel. Some of the characters fit into the immediate justification readers have about a character. Other times, the reader's initial judgement is off.
To define the main theme of the novel, one needs to examine what the novel said to them about the overall message. Therefore, simply decide which theme presented proves to be the one with you, as the reader, most identify with.