Breast cancer is the most prevalent tumour found in women in Australia. Breast tumours are highly heterogenous and are classified into six subtypes based on expression of molecular markers. These subtypes are believed to arise from distinct epithelial cell populations within the mammary gland. Uncovering the molecular mechanisms governing epithelial cells in the mammary gland is vital for the discovery of new targeted therapeutics. Regulation of alternative splicing underpins many developmental processes and is often utilised in cancer to promote oncogene expression and down regulate tumour suppressor genes. We have undertaken a comprehensive analysis of alternative splicing in the three distinct epithelial cells in the mammary gland, basal cells (mammary stem cell enriched), luminal progenitors and mature luminal cells. These data indicate that the mammary gland displays excessive intron retention compared to other murine organs. This intronic retention is mostly restricted to the luminal progenitors. Furthermore, luminal progenitor cells display less complex splicing patterns compare to the basal and mature luminal populations. We believe the cause of this deregulated splicing is the global downregulation of splicing factors in luminal progenitors. Luminal progenitor cells are believed to be the cell of origin for the aggressive basal-like breast cancer subtype, which displays the lowest level of intron retention. Many splicing factors are highly expressed in basal-like tumours, suggesting major differences in splicing events between normal tissue and neoplasia. We are currently investigating the role splicing during the tumourigenesis process through the use of murine mouse models of pre-neoplasia. Basal-like tumours remain difficult to treat given the lack of targeted therapeutics. We aim to uncover critical splicing factors important for basal-like tumour transformation that may provide novel drug targets.