According to the cancer stem cell (CSC) model, higher CD133 expression in tumor tissue is associated with metastasis and poor prognosis in colon cancer. As such, the CD133-positive (CD133(+)) subpopulation of cancer cells is believed to play a central role in tumor development and metastatic progression. Although CD133(+) cells are believed to display more CSC-like behavior and be solely responsible for tumor colonization, recent research indicates that CD133(-) cells from metastatic colon tumors not only also possess colonization capacity but also promote the growth of larger tumors in a mouse model than CD133(+) cells, suggesting that an alternative mechanism of metastasis exists. This study investigated this possibility by examining the cell viability, tumorigenicity, and proliferation and growth capacity of the CD133(+) and CD133(-) subpopulations of the SW620 cell line, a human metastatic colon cancer cell line, in both an in vitro cell model and an in vivo mouse model. While both SW620 (CD133-) and SW620(CD133+) cells were found to engage in bidirectional cell-type switching in reaction to exposure to environmental stressors, including hypoxia, a cell adhesion-free environment, and extracellular matrix stimulation, both in vitro and in vivo, CD133(-) cells were found to have a growth advantage during early colonization due to their greater resistance to proliferation inhibition. Based on these findings, a hypothetical model in which colon cancer cells engage in cell-type switching in reaction to exposure to environmental stressors is proposed. Such switching may provide a survival advantage during early colonization, as well as that explain previous conflicting observations.