ON THE COVER Cancer cells spreading through the circulation. During the last decade, there has been a growing appreciation for liquid biopsy as a diagnostic tool. Liquid biopsy is the analysis of nontissue specimens, usually blood, to look for cancer cells or DNA fragments. This issue of Clinical Chemistry contains three articles covering the analytical validation of liquid biopsy hotspot variant assays, single cell and plasma RNA liquid biopsy for hepatocellular carcinoma, and programmed cell death ligand-1 expression by circulating tumor cells as a biomarker for non-small lung cancer. An accompanying editorial discusses the implications of blood-based analysis of tumor cell DNA and circulating tumor cells. (See pages 1437 and 1483.) Reproduced with permission from Shutterstock/Lightspring