Methods relying on anti-epithelial cell adhesion molecule (EpCAM) for positive affinity-selection of circulating tumor cells (CTCs) has been cleared by the Food and Drug Administration (FDA) for metastatic breast, prostate, and colorectal cancers; however, enumeration of EpCAM(+) CTCs alone has demonstrated modest clinical sensitivity.1 EpCAM-bearing CTCs may not be the only “players” in cancer progression. This evidence concerns the gene EPCAM and colorectal cancer.