The RET fusion kinase appears to be a mutually exclusive oncogenic driver that does not overlap with other known driver mutations such as KRAS, BRAF, EGFR and PIK3CA and oncogenic fusion kinases involving ALK, ROS1 and NTRK. Since we observed a low 0.2% frequency in unselected CRC patients, this mutual exclusivity may facilitate prospective screening for RET fusion kinase in CRC patients who are pan-negative for other known driver mutations. This evidence concerns the gene PIK3CA and colorectal carcinoma.