PURPOSE: Women residing in disadvantaged neighborhoods experience disparities in breast cancer (BC) survival which persist when accounting for individual-level socioeconomic/treatment factors. The chronic stress of living in a disadvantaged neighborhood may compound the stress of a new cancer diagnosis, leading to neuroendocrine dysregulation. Cognitive Behavioral Stress Management (CBSM) has shown efficacy at reducing distress and modulating neuroendocrine functioning, but it is unknown whether it is efficacious in this population. METHODS: This is a secondary analysis of a randomized trial of 10-week group-based CBSM (versus a psycho-educational control) in women with nonmetastatic BC. The Area Deprivation Index (ADI) was calculated, and women were categorized as living in low (n = 175) versus high disadvantage (n = 50). Women completed a measure of cancer-related distress (Impact of Events Scale-Intrusions) and underwent blood draws to collect PM cortisol at baseline, 6 months, and 12 months. Hierarchical linear modeling tested whether condition predicted the slope of outcomes, and whether ADI moderated these relationships. RESULTS: CBSM was associated with greater reductions in cancer-specific distress and cortisol, though these effects were not found to be moderated by ADI. Exploratory simple slope analyses showed that CBSM was associated with decreased cancer-related distress across ADI categories, while CBSM resulted in decreased cortisol among low ADI women only. CONCLUSION: CBSM reduced cancer-related distress across neighborhoods, but this was only accompanied by cortisol changes among those in advantaged neighborhoods. Neighborhood disadvantage may represent a particularly salient stressor that is distinct from cancer-specific distress. Future interventions targeting this population should consider modifications to increase relevance and accessibility.