The identification of CXCR4+ tumor cells as metastasis stem cells (MetSCs) (Oskarsson et al, 2014) in colorectal cancer (CRC; Croker & Allan, 2008; Zhang et al, 2012; Murakami et al, 2013; Wang et al, 2014) allowed us to evaluate the clinical relevance of targeting CRC MetSCs by assessing whether their selective elimination induces antimetastatic activity. Here, CXCR4 is linked to colorectal cancer.