--- - |2 Abstract Breast cancer is linked to psychological distress and mood disorders that are in turn associated with higher psychological dysfunction and decreased breast cancer survival. It is considered that psychological health in breast cancer is considerably affected by body image impairment, which in turn seems to be highly associated with shame. However, the impact of these variables on mental health may not be direct. The current study aimed to explore a comprehensive model regarding the role of chronic illness‐related cognitive fusion in the relationship of body image dissatisfaction and chronic illness‐related shame with depression symptoms. The sample was composed of 75 women with nonmetastatic breast cancer, recruited in a Radiotherapy Service in central Portugal. The conducted path model presented an excellent fit and accounted for 59% of the variance of depressive symptomatology. Further, it demonstrated that body image dissatisfaction's impact on depressed mood is significantly explained by the mechanisms of chronic illness‐related shame and chronic illness‐related cognitive fusion. It was also revealed that chronic illness‐related cognitive fusion additionally mediated the impact of chronic illness‐related shame on depression. These findings are suggestive of the importance of body image and chronic illness shame in the determination of breast cancer patients' depression symptoms and also the central role of chronic illness‐related cognitive fusion in these relationships. Therefore, the implementation of acceptance and defusion‐based psychotherapeutic interventions to improve mental health in cancer patients seems to be of great importance. - Clinical Psychology & Psychotherapy, EarlyView.