Purpose: Many clinical interventions have been designed to improve psychological well-being in women with breast cancer; however, there are individual differences in the extent of benefit across participants. Mindfulness-Based Stress Reduction (MBSR) is a structured 8-week intervention that has been shown to reduce depression and anxiety for patients with breast cancer. Personality factors may influence which participants benefit more from various psychological interventions, including MBSR.Design: In a secondary analysis, we examined whether personality factors accounted for variability in response to an MBSR intervention for women with breast cancer.Sample: Two hundred eighty Danish women with breast cancer who completed the Mindfulness and Cancer Mamma trial were included in this analysis.Methods: Using multiple regression analyses, we investigated whether personality factors, measured by the NEO-PI-R, contribute independently or interact with treatment to predict depressive symptoms at 2, 6, and 12-month follow-up.Findings: The interaction between low conscientiousness and MBSR, as well as high neuroticism and MBSR each predicted significantly lower levels of distress at 12-month follow-up compared to women who higher in conscientious or lower in neuroticism.Conclusions: Personality factors may contribute to the impact of psychosocial interventions, such as MBSR, on psychological well-being.Implications for Psychosocial Providers: Utilizing personality measures may assist providers in identifying which patients may benefit from mindfulness therapies.