American Indian (AI) men have some of the highest rates of colorectal cancer (CRC) in the United States but among the lowest screening rates. Our goal was to better understand awareness and discourse about colorectal cancer in a heterogeneous group of AI men in the Midwestern United States. Focus groups were conducted with AI men (N = 29); data were analyzed using a community-participatory approach to qualitative text analysis. Several themes were identified regarding knowledge, knowledge sources, and barriers to and facilitators of screening. Men in the study felt that awareness about colorectal cancer was low, and people were interested in learning more. Education strategies need to be culturally relevant and specific.