Sherman Alexie depicts the relationship between Native Americans and white Americans as tentative at best and frequently distrustful and even hostile. Both sides often appear to have preconceived notions about the other, which can lead to misunderstandings and negative feelings and sometimes even negative consequences.

For instance, in his book The Absolutely True Diary of a Part-time Indian, he writes about the physical challenges he had at birth and as a young boy. He talks about his dental problems and describes how he needed to have teeth removed to offset the overcrowding in his mouth. His family visited the Indian Health Service clinic situated on the reservation. However, his dental needs were so extensive that Indian Health Service would not fund all the work he needed over a period of time. As a result, he had to have extensive and extremely painful work completed all in one day. When he went to see the families dentist, or as he says, “our white dentist,” he writes about the experience:

“And what's more, our white dentist believed that Indians only fell half as much pain as white people did, so he only gave us half the Novocain.
What a bastard, huh?”

Even the white people who seemingly are there to help are described in terms that convey his sense that these people have ulterior motives. For instance, he calls the white teachers who live on the reservation “liberal, white, vegetarian do-gooders.” His use of sarcasm would seem to imply that he believes they derive a sense of self-fulfillment and perhaps superior feeling by teaching on the reservation. Similarly, he describes the religious among them as “conservative, white missionary saviors.” Using the word “saviors” is another example of sarcasm. Alexie probably does not believe that Native Americans need saving the way that these white "saviors" feel they do.

Given the gulf that exists between the two groups, when the protagonist first transfers to the all white school located off the reservation, his family is nervous and skeptical and his friend Rowdy is angry at him.