Our results suggest the presence of clonal heterogeneity in driver genes, including hotspot mutations, such as APC, TP53, and KRAS. We also found that the number of clonal mutations was much more than that of subclonal mutations in CRC driver genes, indicating that the majority of CRC driver genes are the basis of the tumorigenesis of cancer and tend to exist in the trunk of the phylogenetic tree during the cancer evolutionary process. This evidence concerns the gene KRAS and colorectal carcinoma.