In Indian Killer A lexie uses a pulp-fiction form, the serial killer mystery, to frame the social issues facing American Indians. He populates the book with stock characters such as a grizzled ex-cop, a left-wing professor, a right-wing talk radio personality, drunken bums, thuggish teenagers and a schizophrenic main character who serves as the most obvious suspect in a mystery that never quite resolves itself. John Smith, the troubled Indian adopted by whites appears at first to be the main character, but in some respects he is what Alfred Hitchcock called a McGuffin. The story is built around him, but he is not truly the main character and he is not the heart of the story. His struggle, while pointing out one aspect of the American Indian experience, is not the central point. John Smith's experiences as an Indian adopted by whites have left him too addled and sad, from the first moment to the last, to serve as the story's true focus.

The damage that had been done to John Smith was irreparable from the moment the story began. His death, while a gloomy ending for his character, is in many ways a release from his torment, as demonstrated by his rising from the point of impact and leaving his body behind. The value of John Smith is to serve as an extreme example of the damage being done to Indian society. The heart of the story is the experience of Marie Pol atkin. Unlike the somewhat stock characters that make up much of the mystery element of the novel, Marie is a fully realized and nuanced character. While her views are as passionate as any character in the book, her views are backed by her actions.

It is Marie who faithfully drives the sandwich van, feeding the homeless. It is she who faces down the three thugs who mean to attack the homeless Indians. It is she alone who believes that John Smith is not capable of murder. Marie, first with Dr. Mather, then with the university president and finally with the police restates the central argument of the novel, that white involvement with American Indians is destroying their culture. Marie does not see a difference between the left-wing sympathizers and the right-wing antagonists.

She makes the argument quite clearly that, if the ghost dance had worked, all the whites would have been slaughtered. The dance does not make exceptions for the well meaning. To Marie, any interference is damaging, and the thought of whites co-opting her culture is especially galling. The book points out many different attacks on Indian culture. John's adoption, legal or not, by his kind but misguided parents demonstrates the tragedy that can come from cross-cultural adoption.

The experiences of Marie's cousin Reggie, who has the tapes of his family's stories stolen and co-opted by Dr. Mather (who has convinced himself that he is doing the right thing because the find is anthropologically valuable) demonstrates the wrongs done by intellectuals who only view other cultures in terms of what they can learn from them. Truck Schultz and the three enraged college students demonstrate how quickly the underlying distrust of Indian culture can turn to outright bigotry and violence. Truck Schultz fans the flames with his statements, such as, "The only good Indian Killer is a dead Indian Killer." The college students serve as the freehand instrument of his attacks. The police and the university board demonstrate the damage of well-meaning but ill-advised authority figures. The police do not oppose the Indians, but they do view them with a sort of hesitant confusion.

The police officer who encounters John Smith and the vagrant knows that schizophrenics are not dangerous, but the stories of the Indian Killer keep him from aiding John. When he has a chance to bring him in, he is afraid to chase after him. The university board shows the biases of education.