Cancer is the leading cause of death among American Indian and Alaska Native (AIAN) women, and depressive symptoms have been linked to higher mortality, but research on depressive symptoms among AIAN cancer patients has been scant. The purpose of this exploratory study was, using the Framework of Historical Oppression, Resilience, and Transcendence, to examine risk and protective factors related to depressive symptoms in American Indian (AI) women cancer survivors. We examined the relationships of adverse childhood experiences (ACE), perceived health status, resilience, and social support with depressive symptoms in Northern Plains AI women cancer survivors. We used a cross-sectional design with purposive sampling of 73 female cancer survivors (aged 18 years or older) between June 2014 and February 2015. Hierarchical multiple regression was used to test three sets of variables in relation to depressive symptoms: (1) sociodemographics, (2) risk factors (ACE and perceived health), and (3) protective factors (psychological resilience and social support). Approximately 47 percent of participants had probable depressive symptoms. Depressive symptoms were inversely associated with perceived health, psychological resilience, and social support. These results support bolstering existing social support among AI cancer patients and survivors as well as prevention and intervention efforts that strengthen resilience.