Cathepsin S (CTSS) is a lysosomal protease which is normally associated with antigen presenting cells. However, we and others have shown that it is causatively involved in cancer progression, playing key roles in tumour invasion, angiogenesis and metastasis. Various cell types recruited to the tumour microenvironment can contribute this protease including tumour associated macrophages, endothelial cells and cancer cells themselves. Whilst we have an appreciation of the control of CTSS in the stromal cell types, at this time we do not have understanding of why CTSS is expressed in tumours. To address this, we have studied tumour-specific expression of CTSS over non-stratified breast cancer TMAs, highlighting differential expression patterns. Analysis of the association of CTSS expression and tumour sub-types found that CTSS expression was particularly prevalent in triple negative (ER-, PR- Her2-) tumours. In this talk we will thus discuss the research that we have undertaken to understand the specific molecular basis for the expression of CTSS in these tumours, and the likely impact that CTSS inhibition would have in this type of cancer.