Micro (mi)RNAs are emerging as important regulators of cellular differentiation, their importance underscored by the fact that they are often dysregulated during carcinogenesis. Two evolutionary conserved families, let-7 and miR-200, regulate key differentiation processes during development. Loss of let-7 in cancer results in reverse embryogenesis and dedifferentiation, and miR-200 has been identified as a powerful regulator of epithelial-to-mesenchymal transition (EMT). Recent findings have connected let-7 with stem cell maintenance and point at a connection between EMT and stem cell formation. A part of tumor progression can be viewed as a continuum of progressive dedifferentiation (EMT) with a cell at the endpoint that has stem cell-like properties. I propose that steps of this process are driven by specific changes in the expression of let-7 and miR-200 family members.