While Roth's treatments of the human condition often argue that life makes no sense (see, for example American Pastoral in which Seymour "Swede" Levov, his paragon of decency and convention, learns just that lesson), The Human Stain argues a profound question, one that poets have been examining for thousands of years. How do you know who you are, the Sophoclean question? And what are the consequences of either not knowing or of denying one's identity? At the heart of this thematic question is the related one of knowing and recognizing one's parents. When a parent denies a child or a child denies his parent, the consequences for the individual and society are profound. When Coleman denies his mother because she is black, Roth has created one of the most painful and moving scenes in all his work. Here is the most fateful, intensely painful emotional transaction possible between parent and child. In denying his mother, Coleman ironically denies his own ethnic and cultural heritage and cuts himself off from his family to "pass" as a Jew, which for Coleman is to pass for "white," so that he may avoid the consequences of being black in a racist post-World War II America.

Another equally ancient theme in this novel is the effects of war on individuals and the community. This theme, related to the social concerns analyzed above, is embodied in the character of Lester Farley, a veteran of the Vietnam War who suffers intensely from post-traumatic stress disorder, the disorder from which Odysseus suffered, according to some scholars, and for which he is exiled for ten years before being allowed to return to Ithaca. Supposedly cured by his exile just as Farley has been "cured" by the efforts of counselors, he still wreaks terrible "vengeance" upon his community when he returns to restore himself to leadership of family and community. Apparently, neither veteran has been entirely cured of "the war sickness."

Other classical allusions are woven into the novel. Athena was the goddess of wisdom for the Greeks; she was Odysseus' patron and protectress, but she leaves Odysseus for a period of ten years because he and his men desecrated her shrine during the sack of Troy. Supposedly, Athena is the "patron" of Athena College, but as wisdom she has absented herself from Athena College where Coleman Silk has served as a professor of classics and then as dean of the faculty. Crossroads are a classical locus for fateful actions and decisions; for example, it was at a crossroads far from his home that Oedipus met a cranky old man and killed him, only to learn much later the man was his father. The rural crossroads post office that Faunia Farley cleans twice a week is where Coleman first sees Faunia. The ancient myth expresses much about the complexities of the human condition and of knowing the truth, especially about oneself, and continues to do so in Roth's story. As Sophocles put it, only expiation of blood for blood and banishment can purify a community of the stain that results from patricide and incest. Roth has woven an intricate tapestry on this old and complex theme and invites his readers to consider the ancient Greek story in its new dress.

A number of other themes are likewise related to the social issues of the novel: For instance, the novel illustrates how good values may be perverted by their extreme and unintelligent application; the value of the classic "middle way" as the best means to achieve the good life is suggested by its absence; and the consequences of crossing boundaries and borders are reflected in plot, especially as they result from the choices the characters make. Even the physical setting functions in The Human Stain as it does in most good novels to reinforce the mysteries of borders.

Then there is the theme posed in the novel's title. What is the nature of human nature? What is the "human stain"? What is finally ineradicable? Is it sex? Is it pride? Is it anger? Is it racism? Or is racism merely a consequence of pride and sex and territorial desire? And there is the theme of the Jew and the black, both figured as outcasts and as wanderers in the white-anglo-Christian- American landscape.