Recently, whole-genome molecular profiling of cancers has revealed that breast cancer consists of a number of distinct diseases at the biological level, each of which will require independent research into the most suitable therapy for that patient. In particular, this has long confirmed the clinician's impression that the clinical behaviour of oestrogen receptor (ER)-positive breast cancer can be markedly heterogeneous despite similar levels of expression of the oestrogen receptor. At present, it seems that there are at least two distinct diseases of luminal origins. In the future, it is likely that we will be treating the luminal-A tumours, characterised by high expression of the ER and related genes, differently from the non-luminal-A tumours, which are characterised by low expression of the ER and related genes, high expression of proliferation genes and a poor clinical outcome. This article reviews the progress thus far in producing a framework for defining the ER-positive luminal subtypes and for our current understanding of the genetic aberrations that may be contributing to the poor prognosis of the non-luminal-A breast cancers.