Precision cancer care aims to develop new therapies and biomarkers based on each patient’s individual molecular tumor profile, but such profiles are difficult to generate from tumor biopsies because of cost, access, and patient safety. Liquid biopsies offer an attractive alternative. The USC Norris Liquid Biopsy Research Core (LBC) is a state-of-the-art, multi-platform facility for the capture and analysis of all liquid biopsy components. The LBC employs a variety of technologies that enrich rare circulating tumor cells (CTCs) for enumeration, phenotypic and/or molecular characterization, together with methods for comparative genomic profiling from matched plasma. The mission of the LBC is to assemble a state-of-the-art, multi-platform facility for capture and analysis of peripheral blood CTCs and matched plasma nucleic acids, and to make this technology and expertise available to USC Norris members.