Indigenous people have experienced a combination of historical injustice, colonialism, and racism, which have resulted in health disparities. Data systems used to statistically quantify these inequities do not adequately account for these experiences and thus inadvertently impact meaningful use of this information to guide cancer treatment decisions and interventions in this patient population. To understand the Indigenous cancer experience, one must understand the inherent flaws in the data used to collect information about Indigenous people, the current state of cancer in Indigenous people, and consider special circumstances in this patient population to guide the path forward in appropriate cancer care, especially surgical care. This chapter will demonstrate that Indigenous populations in the United States (US) (American Indian and Alaska Native—AI/AN) and Canada (First Nations, Metis, and Inuit) experience unique cancer journeys that require unique cancer solutions. Definitions: where appropriate, the word Indigenous will be used pertaining to all Native communities from Canada and the US; however, when possible, distinctions-based terminology will be deployed when referring to findings that are specific to a community or group. In this case AI/AN when referring to Indigenous persons from the US and First Nations, Metis, and Inuit when referring to Indigenous persons from Canada.