Breast cancer patients can have biopsychosocial changes induced by distress related to the cancer diagnosis. This study investigated psychological characteristics and hypothalamic-pituitary-adrenal (HPA) axis function associated with depressive symptoms in breast cancer patients at the initial diagnosis.Seventy-eight breast cancer patients were enrolled, and 61 patients were included in the final analysis. Patients were evaluated concerning psychological adjustment to cancer diagnosis, self-concept and depressive symptoms and given a dexamethasone suppression test before the main surgical treatment.Self-concept scale scores and fighting spirit factor scores of the Korean version of the Mental Adjustment to Cancer (KMAC) scale showed inverse correlations. Anxious preoccupation (AP) factor scores of the KMAC scale positively correlated with depressive symptom scores. Depressive symptom scores were significantly correlated with postdexamethasone serum cortisol levels. In multiple regression analysis, postdexamethasone serum cortisol and the KMAC-AP factor score had significant partial effects in the final model.Hypothalamic-pituitary-adrenal axis dysfunction and anxious coping to cancer diagnosis may be associated with depressive symptoms in breast cancer patients before treatment. Based on this analysis, we recommend psychotherapeutic interventions to increase adaptive mental coping strategy and to ameliorate psychological distress. Screening for HPA axis dysfunction and provision of depression treatment may prevent breast cancer patients from developing depressive symptoms.