There is a large body of literature on immune reactivity to mouse mammary tumor virus (MMTV) during mammary tumor progression. It is a general consensus that MMTV is antigenic and elicits cell-mediated and humoral immune responses. In addition, activation of non-specific inflammatory cells has been observed in various mouse preneoplastic and neoplastic mammary lesions. How these non-conventionally activated inflammatory cells affect tumor progression is a subject of debate. The discovery of MMTV associated superantigens solved certain long standing mysteries and may provide new insight into the cause of these unusual host responses. In this article, we will discuss how superantigen associated secondary immune responses may contribute to mammary tumor progression and the possible impact superantigen may have on specific anti-MMTV reactivity.