In the past two decades interferons have undergone extensive phase I and II evaluations in various types of cancers, including breast cancer. This article reviews the experience, obtained from preclinical and clinical studies, about the clinical rationale efficacy and toxicity of interferons in cancer treatment. In particular, we examine the preclinical experience in which antineoplastic activity of interferon against breast cancer has been demonstrated. Finally we discuss clinical data accumulated using interferon-alpha, interferon-beta and lymphoblastoid interferon alone or in combination in metastatic breast cancer patients. The use of the interferons in the treatment of breast cancer remains investigational and the optimal scheduling undetermined. New methods of administration may maximize the antitumor effects in order to better understand the role of interferon in clinical oncology.