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Although initial events in colorectal carcinogenesis are relatively well characterized and treatment for early\u2010stage disease has significantly improved over the last decades, the mechanisms underlying metastasis \u2013 the main cause of death \u2013 remain poorly understood. Correspondingly, no effective therapy is currently available for advanced or metastatic disease. There is increasing evidence that colorectal cancer is hierarchically organized and sustained by cancer stem cells, in concert with various stromal cell types. Here, we review the interplay between cancer stem cells and their microenvironment in promoting metastasis and discuss recent insights relating to both patient prognosis and novel targeted treatment strategies. 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