Using a skin window (SW) procedure, we evaluated post-operative cell-mediated immunity (CMI) to autologous breast cancer with reference to its prognostic significance, the nature of the immunogen, and the therapeutic implications. It appears that SW reactivity to autologous breast cancer is prognostically favorable per se and is independent of the prognostic significance of the nuclear grade of the cancer cells; SW reactivity to autologous breast cancer reflects CMI to a determinant(s) that is expressed by glycoprotein 55, the principal envelope glycoprotein of the RIII-murine mammary tumor virus; the glycoprotein 55-like CMi determinant(s) is more regularly expressed by preinvasive than by invasive breast cancers; tumor antigenicity and host reactivity may vary independently; and postoperative monitoring of CMI to autologous breast cancer is prognostically and therapeutically important.