For instance, blood is collected at a patient’s home for ctDNA analysis, then a medical oncologist can adjust the therapeutic plan. These advantages include: i) increased safety since only a routine blood draw is required ii) faster assay turn-around time since there is no need to schedule and coordinate a small operation or image-guided invasive procedure iii) the potential ability to assess the heterogeneity of the malignant process, meaning assessing DNA from both the primary tumor and metastatic foci iv) longitudinal testing prospects with time-based analyses that have not been possible before primarily due to patient safety issues and v) new treatment monitoring strategies. It is important to recognize the advantages of liquid biopsy assays versus traditional solid tumor approaches. Four years later there were two FDA approvals for liquid biopsy tests that were NGS-based 2, 3. The first liquid biopsy assay approved by the FDA in 2016 was PCR-based 1. Liquid biopsy science and clinical applications are progressing rapidly. The data and methods from this study represent a seminal piece of infrastructure for future validation of liquid biopsy methods and tools. Our corresponding proficiency study addresses the accuracy and reproducibility of ctDNA assays using a unique set of reference materials, associated analytical frameworks, and suggested best practices. NGS can also be used to detect DNA shed by a tumor into the blood (aka liquid biopsy (LBx)). This can lead to more specific and individualized treatments. Precision oncology utilizes next generation sequencing (NGS) of tumors for the detection of mutations that cause cancer. Eventually the clinical utility of ctDNA assays is required and our proficiency study and corresponding dataset are needed steps towards this goal. It is the most comprehensive public-facing dataset of its kind and provides valuable insights into ultra-deep ctDNA sequencing technology. The generated dataset encompasses multiple key variables, including a broad range of mutation frequencies, sequencing coverage depth, DNA input quantity, etc. The study used tailor-made reference samples at various levels of input material to assess ctDNA sequencing across 12 participating clinical and research facilities. The SEQC2 Oncopanel Sequencing Working Group has developed a multi-site, cross-platform study design for evaluating the analytical performance of five industry-leading ctDNA assays. With the rapid adoption of ctDNA sequencing in precision oncology, it is critical to understand the analytical validity and technical limitations of this cutting-edge and medical-practice-changing technology. Recently we reported the accuracy and reproducibility of circulating tumor DNA (ctDNA) assays using a unique set of reference materials, associated analytical framework, and suggested best practices.