By comparing the mutation frequency of highly mutated genes, we found that the mutation frequency of APC and TP53 in left‐sided CRC was significantly higher than that in right‐sided CRC, while the mutation frequency of PIK3CA, ACVR2A, FAT4, and RNF43 in right‐sided CRC was significantly higher than that in left‐sided CRC. Here, RNF43 is linked to colorectal carcinoma.