Assessment of somatic genomic alterations from tumors can now be performed by sequencing circulating tumor DNA from the cell-free component of blood. This procedure, which identifies tumor-derived somatic mutations from a simple blood sample, circumvents the need for tumor tissue. A recent study highlights the promise of circulating tumor DNA to guide therapeutic decisions in a variety of solid tumors for both clinical and investigative purposes, as well as providing a tool for the early detection of cancer.