Introduction: Despite the various therapeutic combinations and the emergence of new targeted therapies, there is still no curative treatment for all stages of colorectal cancer. Through the query for the best possible combination and solution, a new theory approaching colorectal cancer as a stem cell disease appeared, with a continuously growing body of evidence supporting this idea. The inability to directly recognize cancer stem cells has led researchers to an attempt of distinguishing those using indirect markers.
Discussion: This review focuses on colon cancer stem cell theory, the various findings supporting and contradicting this hypothesis, and the markers used up to now in characterizing stem cell populations in colorectal cancer. Despite the numerous unanswered questions on this new cancer hypothesis, it appears to have a justifiable role to play in colorectal cancer tumor biology, and furthermore, it may be the basis for the development of new therapeutic agents of the future. Therefore, every surgeon, oncologist, and physician who is implicated with this disease should be familiar with this novel colorectal cancer theory.