The purpose of this study was to evaluate a woman's psychological and immunological response to breast biopsy before and after the procedure. Women were enrolled into the study when notified of the need for breast biopsy. Psychological and immunological assessments were made at enrollment, on the day of breast biopsy, as well as 1 month and 4 months after notification of biopsy results. Psychological assessments demonstrated that perceived stress, anxiety, and mood disturbance were heightened before biopsy and remained elevated after biopsy regardless of the diagnosis. Immunologically, the women exhibited reduced natural killer cell activity and INF gamma production before biopsy with reductions significant 1 month after the procedure. In contrast, IL-4, IL-6, and IL-10 production were increased before and after the procedure with most significant increases prior to the procedure and continuing 1 month after the procedure. These results demonstrate that undergoing biopsy of the breast for cancer diagnosis is an emotional experience, characterized by increased perceived stress, anxiety, and mood disturbance. This emotional distress is accompanied by reduced NK cell activity and cytokine dysregulation. The psychological and immunological impact of breast biopsy is not transient, but persists well beyond the actual experience of the biopsy procedure. Noteworthy is the observation that women with benign or malignant biopsy results experienced similar psycho-immune consequences. Hence, these observations are of relevance not only to women diagnosed with malignancy, who face the challenges of cancer treatment and adaptation to illness, but also to women with benign biopsy findings.