The juxtaposition of Chippewa beliefs with Christianity, specifically Catholicism, forms the most significant theme in the novel. The survival of the Chippewa people directly correlates with the adherence to their old ways, while accepting the white way of life, including Christianity, dooms the Chippewa people to extinction. Though the young priest, Father Damien, understands and works strenuously as an advocate for the native people, he has a limited ability to make a difference within the Chippewa’s lives. Others are not so friendly to the native way of life. For example, to become a nun, Pauline must repudiate her Chippewa blood and claim to be entirely white. She does this willingly after a vision in which Jesus tells her that she carries no Chippewa blood and is white.

Those who stick to the old ways and the old medicine, such as Nanapush, survive. Though all of his family is taken from him, including four wives and two children, Nanapush adheres to the old ways and survives, even as he also learns the ways of the white government with its forms, papers, and letters.

He adopts Lulu to ensure that the Nanapush line does not end with him.