The reliability of IHC staining for the expression of driver mutations performed on 2 (2mm) TMA cores versus the original tissue sections was investigated on a series of 60 selected blocks from lung neoplastic lesions including 23 blocks carrying ALK gene fusion, 12 with ROS1 gene fusion, 3 with NTRK1 gene fusion, and a series of 12 blocks from selected colorectal carcinomas with absence of mismatch repair protein expression in 7 cases. The gene discussed is ALK; the disease is colorectal carcinoma.