Background: Translation of underlying individual genomic heterogeneity in cancer into precision medicine practice requires annotated cancer biorepositories. An overview of experience and outcomes of Mayo Clinic Cancer Center Genito-Urinary (GU) liquid biobank established since 2009 is presented. Methods: An institutional ethics approved prospective liquid biorepository was established in 09/2009 for advanced GU cancer patients visiting Mayo Clinic. Informed consent approved collection of 29.5 ml blood/urine was performed serially on enrolled patients and clinical annotation was obtained during follow up including previous, current and future treatments and their outcomes. All specimens were processed using a uniform protocol in which extraction of germline DNA from buffy coats; serum for proteomics; platelet poor and platelet rich plasma (in citrate and EDTA anticoagulants) for microRNA and cell free DNA extractions; and extraction of PAXgene RNA/DNA from whole blood was performed. Processing was done within 45 minutes of sample acquisition and storage in -80C freezers with no freeze-thaw cycles. Results: Between 9/2009 and 01/2015, 535 advanced stage prostate cancer patients in hormone sensitive and castrate resistant stage; 250 advanced kidney cancer patients; 110 testicular cancer patients were enrolled and 1550 collections were performed serially. This generated >60,000 plasma/serum/DNA/RNA aliquots. Nucleic acids (DNA/RNA) from buffy coats and whole blood of 500- 1000 ng volume each were also extracted. Cell free DNA for somatic mutational and copy number analysis; single nucleotide profiling from germline DNA; RNA expression profiling from whole blood and microRNA analysis in plasma has been performed from this cohort along with proteomics using tandem mass spectrometry. By 2017, this has resulted in >35 publications; 5 patents; multiple national grant awards and enhanced precision cancer care.