A large number of studies suggest that beside tumor autonomous abnormalities, tumor-microenvironment interactions may affect tumor growth and metastasis formation. Inflammatory cells, primarily macrophages may affect tumor development and progression by their ability to express a large variety of factors, including inflammatory cytokines. One of these cytokines is tumor necrosis factor alpha (TNFalpha ). TNFalpha is a primary mediator in the pathogenesis of infection, injury and inflammation. It is involved in the beneficial processes of host defense and tissue homeostasis. The net biological effects of TNFalpha may ultimately benefit or injure the host, depending on its concentration, duration of tissue exposure and the presence of other mediators in the cellular environment. TNFalpha may exert anti-tumor and protumor activity. These effects have been examined in various experimental models and in different clinical settings. In this article we discuss the anti-tumor and protumor activities of TNFalpha with a special reference to breast cancer.