Prostate cancer is the most diagnosed internal malignancy in the western world. While the majority of prostate cancers are non-lethal, there is currently no reliable approach to distinguish lethal from non-lethal prostate cancer at an early, curable stage. Over the last 7 years, researchers at Epworth Medical Centre and Royal Melbourne Hospital have compiled a bio-bank of over 1500 tumour specimens to better understand the underlying molecular mechanisms governing lethality in prostate cancer. Along with excellent clinical information, the bank contains many individuals that have matched whole-blood, primary tumour and distant metastases. This provides a unique resource for molecular profiling to help understand lethal prostate cancer. Dr Chris Hovens and his group at Royal Melbourne Hospital have carried out molecular profiling of a number of samples using RNA-SEQ, Illumina 2.5M SNP Chip, whole-genome sequencing and Illumina 450K methylation chip. In collaboration with NICTA, VLSCI, and the Welcome Trust Sanger Institute, bioinformatics analysis of this data is currently underway. Samples from two individuals have been analysed so far: whole-blood, primary tumour and castrate resistant metastasis in patient 1 and whole-blood, primary tumour, local recurrence, two hormone naive metastases, and a castrate resistant metastasis in Patient 2. Single nucleotide variants, small insertion/deletions, copy-number variations, differentially expressed genes and differentially methylated regions are being used to uncover the molecular mechanisms driving progression to metastasis and treatment resistance. This study highlights the benefits of an integrated genomics approach for tracking the progression of a tumour in a given individual.