The prevalence of stress-and-anxiety related comorbidities is increased 3-fold in cancer patients compared to the general population. This has been attributed to the stress of a cancer diagnosis, the impact of cancer treatments like chemotherapy and the fear of cancer reoccurrence. However, the incidence of anxiety-and-stress disorders is increased in the months prior to a cancer diagnosis, when patients plausibly have developed tumours, but are unaware of it. This begs the question whether the increase in stress disorders in cancer patients at diagnosis is casually linked to the impact of both cancer and the psychological distress of receiving a cancer diagnosis on the brain. Cancer and stress may share inflammatory brain mechanisms that contribute to stress disorders in patients. Astrocytes and microglia are immunoreactive cells of the brain that respond to inflammation, a hallmark of cancer, and stress. Using a mouse model of breast cancer, we compared the impact of mammary tumours and chronic stress on microglial and astrocyte reactivity throughout regions of the brain critical for anxiety and stress coping. For the first time, we show that cancer and chronic stress activate microglia to the same extent in the same subcortical brain regions, which correlates with worse stress coping behaviours (all p < 0.05). The findings suggest that the sensitizing effect of cancer to stress in brain regions important for interpreting and responding to psychological distress may contribute to the high incidence of stress disorders in cancer patients. In contrast, cancer reduced astrocyte reactivity in the cortex (p < 0.05) where no changes were observed in response to chronic stress. Together, these findings suggest that (1) the impact of cancer on glia are cell and brain-region specific and (2) cell-specific interventions that suppress microglial activation or stimulate astrocyte reactivity may be required to treat stress disorders in cancer patients.