The relationship between cell-mediated immunity (CMI) to autologous breast cancer tissue and subsequent clinical behavior has been studied by one of the authors since 1953. In this article the prognostic significance of CMI as measured by a skin window (SW) procedure is reported. The procedure examines cellular responses to coverslip-mounted sections of autologous breast cancer tissue that have been applied to a microabrasion of the skin. Using criteria routinely employed in conventional hematologic and pathologic diagnoses, diverse patterns of SW responses can be identified. Specific patterns are recognizable that are consistent with CMI and that vary significantly with stage and subsequent behavior of the disease. Intrastage variations in behavior were found for patients with invasive breast cancer according to nuclear grade (NG) and postoperative SW reactivity to autologous breast cancer. Positive SW reactivity was associated with a significantly reduced risk of metastases and also appeared to impede the occurrence of metachronous second primary invasive breast cancers. The findings demonstrate the current value of NG and SW response characteristics with regard to prognosis and immunotherapy. Moreover, they are consistent with the development of immunoprophylaxis.