Many cancers in American Indians (AIs) are not diagnosed early leading to effects on physical, social, and emotional well-being or quality of life (QOL). Little research has been done on QOL of AIs in Oklahoma. This study examined the experience of living with cancer of AIs in Oklahoma to gain greater understanding of QOL issues and provide a basis for interventions to improve QOL. Twenty AIs diagnosed with cancer and receiving care in Oklahoma participated in this pilot study through semistructured interviews. Data were analyzed using thematic analysis. Themes identified included circles of support, finding meaning in the experience, and facing personal challenges such as health care–related issues, including mental health needs and fragmented care. The findings from this pilot study provide insights into the cancer experience of AIs in Oklahoma and demonstrate that care navigation and social support are important aspects to address in intervention development.