Stemness characteristics are defining properties of cancer initiating cells and are associated with the ability to metastasize and survive in hostile environments. Establishment of the stem cell network depends on the action of a set of core transcription factors that work in concert with other ancillary proteins that are also important during embryonic development. New data consolidate the role of core pluripotency transcription factors OCT4, SOX2 and NANOG as adverse prognostic factors in colorectal cancer. mRNA-binding proteins LIN28 and Musashi, that are associated with stemness, and epigenetic modifiers such as de-acetylase SIRT1 may also have prognostic value in colorectal cancer. This paper provides an update of the stem cell factors in the pathogenesis and prognosis of colorectal cancer.