Despite inactivating APC mutations, colorectal cancers express the WNT-effector protein β-catenin in a heterogeneous pattern, with strong nuclear expression confined to a fraction of tumor cells, often only at the tumor's leading edge. WNT-reporter constructs allow separation of these tumor cells with highest WNT/β-Catenin activity, which also express high levels of several putative cancer stem cell antigens. Unexpectedly however, these cells do not show exclusive tumorigenicity in xenograft experiments, thus questioning their general stemness phenotype. Instead, there appears to be significant plasticity between both tumor cells with high and low WNT/β-Catenin activity because both cell types can form tumors which again show mixed populations. Furthermore, WNT/β-Catenin activity in colon cancer cells can be modulated by MAPK signaling thus revealing a means of how other signaling pathways contribute to WNT signaling plasticity in colon cancer.