Like much of Philip Roth's fiction, Goodbye, Columbus features central characters who assert their individuality but feel strong ties to a heritage about which they are nonetheless ambivalent. The theme of class conflict is important in the story. Neil's basically working-class background contrasts with the nouveau-rich upward mobility of Brenda's family. When his relationship with Brenda begins, he feels under pressure to "do something" with his life instead of working in a library as he does. He's alienated by the implicit judgment of Brenda's parents that because he has not made a "success " of himself, he's not acceptable for their daughter. And his overall value system is different from theirs. His affair with Brenda, though it's happening in the Patimkin house, is a secret from the parents, and when they find out about it, the relationship is over. Brenda herself, though burdened by the harsh criticisms of her mother, is in some sense more loyal to the parents than to Neil. She doesn't believe she's done anything wrong, but can't commit herself to the rejection of older values and the individuality Neil represents.

A significant theme is that Neil, though a freethinker in religion, is still more connected to his Jewish background than Brenda is with her wealthy parents in suburban Short Hills. When Neil understands the word gonif (thief), Mr. Patimkin remarks that "you know more than my kids." The story as a whole is a depiction of the changing world at the start of the 1960's in which the relative value of old and new is being questioned and re-interpreted.

One of the most important themes of the stories is class differences.  Since Neil and Brenda are from different social classes, they do not have an equal relationship.  Neil, who is poor, cannot see himself as an equal to Brenda's richer family and considers himself in competition with them.