The heart of any biomarker is in its clinical utility. Since 1948, when Mandel and Metais first described the presence of cell-free DNA (cfDNA) in the circulation6, there has been a slow but steady increase in the number of publications demonstrating the potential clinical applications of these molecules. The most successful efforts to date have been in noninvasive prenatal diagnostics, where the genetics of a fetus can be assessed from cfDNA in expecting mothers. These developments have recently catapulted cfDNA into the clinical arena, and several companies are currently bringing this diagnostic application of cfDNA to patients. The exploration of cfDNA from the tumors of cancer patients, termed ctDNA, as a viable biomarker has overcome several obstacles in the recent years thanks to the advent of digital genomics. The digital analysis of DNA sequences allows the highresolution detection of mutations, especially rare ones that are otherwise unappreciated in admixtures of wild-type and mutant DNA7. Several groups have now reported that mutations