Background and context: First Nations, Inuit and Métis bear a disproportionate burden of cancer in Canada. In the spirit of truth and reconciliation, and to have the greatest impact, it is important for nonindigenous and indigenous partners to work together, and reflect on lessons learned in collaborating, to support First Nations, Inuit and Métis health and wellness. Aim: In response to the national Truth and Reconciliation Commission Calls to Action, the Canadian Partnership Against Cancer committed to understanding how collaborative projects funded through the Coalitions Linking Action and Science for Prevention (CLASP) initiative were successful in bringing together diverse groups - both indigenous and nonindigenous - to create and apply culturally-relevant cancer prevention approaches. Strategy/Tactics: Seven projects funded through the CLASP initiative, from 2009 to 2016, brought together over 275 First Nations, Inuit, or Métis communities, schools, and organizations with government, nongovernment, and academic partners in collaborative coalitions. The projects addressed cancer prevention issues prioritized by First Nations, Inuit, and Métis (e.g., unhealthy eating and physical inactivity) through approaches that were holistic and culturally-relevant, such as utilizing intergenerational knowledge sharing, incorporating mental wellness, and supporting existing capacity within communities. Program/Policy process: Over 30 knowledge products developed by the projects were reviewed to identify preliminary lessons learned about partner collaboration. Preliminary lessons learned were verified and expanded upon through nine key informant interviews with CLASP partners. Key informant interviews were informed by four advisors representing indigenous and nonindigenous leaders and partners. The refined set of lessons learned were finalized through qualitative analysis and validated through a conference session and one-day workshop with CLASP partners and First Nations, Inuit, and Métis community leaders. Outcomes: Twenty-seven lessons learned that describe how nonindigenous and First Nations, Inuit and Métis CLASP partners worked together to develop and put into practice culturally-appropriate cancer prevention approaches were identified. The lessons learned were grouped into six themes: 1. respectful relationships; 2. engagement with indigenous communities; 3. addressing accountability requirements, decision-making, and governance; 4. community direction; 5. supports and resources; 6. communication and knowledge exchange. What was learned: The actionable lessons learned are intended to guide future relationship building and engagement between nonindigenous partners and First Nations, Inuit and Métis partners. It is intended that these lessons will be beneficial to collaborative cancer prevention efforts around the world and inform broader system change leading to a reduction in indigenous cancer burden disparities.