ON THE COVER Cancer Cells. This image depicts circulating tumor cells (CTCs) in peripheral blood. CTCs, which originate in primary tumors, recurrences, or metastases, are biomarkers for noninvasively measuring the evolution of tumor genotypes during treatment and disease progression. CTCs are important because the majority of deaths from cancer are linked to the development of disseminated metastases. Published studies have shown that CTCs can be isolated in patients at relatively early stages of tumor growth. Most current methods are based on epithelial cell adhesion molecule (EpCAM) detection, but numerous studies have demonstrated that EpCAM is not a universal marker for CTC detection. Are there alternatives to EpCAM? Yes. This issue of Clinical Chemistry contains a review article that describes the most recent EpCAM-independent methods for enriching, isolating, and characterizing CTCs, on the basis of physical and biological characteristics, and points out their main advantages and disadvantages. (See page 571.) ©Getty Images. Contributor: adventtr. Reproduced with permission.