c-kit (CD117) is a growth factor receptor of the tyrosine kinase subclass III family, normally expressed in a variety of human tissues. Gain-of-function mutations of the c-kit gene have been identified that produce ligand-independent activation of c-kit and cell proliferation. Some of these mutations appear causative in the pathogenesis of adult mastocytosis and most gastrointestinal stromal tumors (GISTs). c-kit receptor and its ligand have been demonstrated in human colon cancer cell lines. Some studies have shown high frequency of c-Kit overexpression in stage II colon cancer patients (59.3%) with significant correlation between c-Kit overexpression and reduced disease free survival. However, other studies failed to demonstrate c-kit expression in a significant number of colorectal cancers suggesting that c-kit kinase activation is not a prominent pathogenetic feature of colorectal cancers. Role of c-Kit continues to be studied in colon cancers.