Breast cancer can be divided into two types according to the estrogen receptor (ER) level of the tumor: ER-positive and ER-negative. Two hypotheses have been raised about the relationship between ER-positive and ER-negative breast tumors. One hypothesis considers ER status as an indicator of a different stage of the disease. The other regards ER-positive and ER-negative tumors as different entities. For both etiological and biological studies of breast cancer it is important to know which hypothesis is correct. In this paper, we review evidence for and against each hypothesis and suggest issues to be addressed in future studies.