Identification of cancer-causing mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, has well-defined and actionable implications for disease prevention. Routine diagnostic BRCA1 and BRCA2 gene screening is expensive and up to 90% of these genetic tests do not return a positive result, suggesting that the current selection criteria for genetic testing are inefficient. Furthermore, ~15% of these tests identify a DNA sequence variant that is of unknown clinical significance, creating a significant challenge for counselling and clinical decision making. These challenges will increase significantly as genomic technologies transform clinical diagnostics. We aim to exploit a powerful new mRNA in situ hybridisation technology to develop an innovative method for prioritising patients for mutation screening and evaluating genomic sequencing results. Moreover, our study has the potential to identify tumours from both familial and sporadic forms of breast cancer that may respond to drugs targeting altered BRCA1/2 genes and related pathways.