There are six major themes in Willa Cather's "Paul's Case":
the "American Dream", deception, choices and consequences, beauty, alienation, and limitations and opportunities.

You can find out much more about each of the individual themes by visiting the eNotes link below.

Here is a brief excerpt which speaks to the overarching theme of the novel:

The story's major themes revolve around questions about Paul's character. Was he driven to his fate by the destructive values of America, or is he morally corrupt, responsible for his actions? Is Paul, as his teachers, father, and friends agree, a ' 'bad case,'' an abnormal personality, or do the others have an overly narrow view of what is "normal"? Do the worlds of business and industry, represented by Cordelia Street, destroy appreciation of culture and aesthetics, or does Paul choose to live in a world of illusion, destroying his grip on reality?