Distinctive pathological and cytogenetic alterations distinguish familial BRCA1 and BRCA2 mutation-positive (+) from sporadic (non-familial) breast cancers. Using cDNA microarrays containing 6,500 sequence-verified human cDNAs, we have compared familial BRCA1 and BRCA2 (+) and sporadic breast cancer patient tumours with a common reference. Relational analyses of individual genes across all experiments has identified a small subset that is consistently up- or downregulated in most BRCA2s and unchanged in most BRCA1 tumours. Similarly, we have identified a set of genes consistently up- or downregulated in most BRCA1 tumours and unchanged in BRCA2 tumours. Analysis of the degree of similarity between expression profiles for the entire gene set across all tumours showed that the BRCA2 tumours form a unique cluster. Visualization of the extent of similarity was performed using multidimensional scaling analysis. Statistical analysis of these data has identified a subset of genes that distinguish the BRCA2 tumours from the BRCA1 and sporadic tumours. The genes identified include several known from previous studies to be implicated in hereditary breast cancer, as well as others previously unrecognized as transcriptionally altered in this disease. An example of a gene in this subset includes that encoding cyclin D1, which was consistently upregulated in BRCA2 tumours, whereas it was unchanged in the BRCA1 and sporadic tumours. Cyclin D1 expression had not previously been correlated with BRCA1/2 mutation status. It is known, however, that cyclin D1 overexpression is positively correlated with estrogen receptor (ER) status, and in our sample set all BRCA2s were ER positive, whereas all BRCA1s were ER negative. This work suggests that investigation of the transcriptional networks of breast cancers can identify genes that clearly distinguish BRCA2 (+) patient tumour biopsies, and indicates this approach will have significant value in ‘molecular fingerprinting’ of breast cancers. We are currently confirming the microarray results and investigating the biological and pathological significance of the other genes identified as key discriminators of BRCA2 tumours.