EPCAM and melanoma: For example, immunoaffinity-based approaches are predominately targeted towards the cell-surface antigen EpCAM.11–13 However, EpCAM has been shown to be downregulated in CTCs during an epithelial-to-mesenchymal transition (EMT), in which these cells adopt a more mobile phenotype that confers a metastatic advantage.14 In melanoma, EpCAM expression is completely absent since melanocytes originate from the neural crest and not the epithelium,15 which magnifies the difficulty of enrichment and detection of target cells.