Abstract Rationale: Lung cancer screening (LCS) can reduce mortality in individuals with a high-risk smoking history, but uptake has been uneven and suboptimal. In our catchment area of Washington state, urban American Indian/Alaska Natives (AI/AN) and sexual and gender minorities (SGM) have high rates of commercial tobacco use and lower uptake of LCS. Mixed-methods community-engaged formative research with both populations revealed barriers to LCS related to social determinants of health, and interest in identity-tailored approaches to LCS care. We used this to develop tailored navigation approaches to LCS. Our study objective was to pilot and evaluate patient navigation programs to facilitate LCS uptake and care completion for these community members. Methods: We conducted parallel LCS navigation pilot studies, with participants who self-identified as AI/AN or as a member of SGM communities and who were LCS screen eligible. Participants were recruited through referrals to our multi-site university-based LCS program, community-based organization partnerships, outreach, and social media. Dedicated patient navigators were trained on LCS processes, navigation, and community-specific best practices. Navigation was guided by handbooks with barrier-specific resources, standardized scripting for contact points, and community-based resources specific to the populations. Participants completed pre- and post-navigation (1-3 months after enrollment) surveys and were followed for LCS uptake, outcomes, and navigation activities through chart review. Results: Between July 1, 2023 and February 1, 2024, 40 participants were enrolled in the navigation pilot studies, 21 in the AI/AN arm and 19 in the SGM arm. The median age of participants was 65 (interquartile range (IQR): 59-69), 80% reported current smoking, and 65% reported a household income below $30,000. Most (55%) reported at least one barrier that delayed access to healthcare in the past year. After enrollment, 35% completed LCS within one month and 55% completed LCS to date. Participants who completed post-surveys (n=22, 55%) indicated that the patient navigator was helpful. Common navigation activities included scheduling assistance, understanding screening results, addressing financial issues, and smoking cessation. Overall, participants approved of navigation approaches with a median Acceptability of Intervention Measure score of 5/5 (IQR: 4.8-5) and a median Patient Satisfaction with Interpersonal Relationship with Navigator score of 44.5/45 (IQR: 39.3-45). Conclusion: These single-arm pilot trials suggest tailored navigation for LCS for AI/AN and SGM communities is a useful approach to engage patients and address barriers and appears acceptable and welcomed. However, substantial variation in LCS completion may reflect complex barriers not addressed through navigation. Community-based and tailored navigation offers a promising approach to address LCS disparities, though further bi-directional refinement of patient navigation is necessary to optimize engagement and LCS completion. Citation Format: Ursula Tsosie, Katie DeCell, Nicolas Anderson, Madison Snidarich, Brandon Omernik, Nicholas Murphy, Matthew Triplette. Community-based lung cancer screening navigation for populations at high risk [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A158.