There is still great controversy as to whether mouse mammary tumor virus (MMTV), the etiological agent of mammary cancer in mice, or a closely related human retrovirus, plays a role in the development of breast cancer in humans. On the one hand, retroviruses such as human T cell lymphotropic virus (HTLV) and human immunodeficiency virus (HIV) are known causative agents of cancer (in the case of HIV, albeit, indirectly) but attempts to associate other retroviruses with human cancers has been difficult. A recent, high profile, example has been the postulated involvement of another mouse virus, xenotropic murine leukemia virus-related virus (XMRV), in human prostate cancer which is now thought to be due to contamination. Here we review some of the more recent evidence for and against the involvement of MMTV in human breast cancer and suggest future studies that may allow a definitive answer to this conundrum. © 2013 Wiley Periodicals, Inc.