On the basis of the similarities of Lef1-deficient Apc-mutant adenomas with Kras-mutant CRC, we propose that Kras and Lef1 act in the same pathway in the process of transformation of ISCs to promote (Kras) or reduce (Lef1) the fixation of mutated crypts. The gene discussed is LEF1; the disease is colorectal carcinoma.