Project Abstract Data on the healthcare experience of Two-Spirit and LGBTQIA+ Native Americans are extremely limited, particularly when it comes to cancer prevention, screening, and care. The limited research available, however, indicates that Two-Spirit and Native American LGBTQIA+ community members encounter more challenges when seeking cancer care. Further, the legacy of ongoing colonization also manifests in unequal social determinants of health, which any intervention must be able to address. In the US, a majority Native Americans live in urban areas. The objective of this project is to focus on adapting the colorectal cancer screening curriculum (NCI-S2S) with and for Two-Spirit and Native American LGBTQIA+ urban populations using a rigorous research methodology that culturally adapts an Indigenized NCI S2S materials for Two-Spirit and Native LGBTQIA+ communities in an urban setting. This project serves as a community-based mechanism to review, understand, and adapt colorectal cancer screening education for next step intervention and delivery across off-reservation Native centers and urban Indian Health Services that serve Indigenous populations in urban contexts.