The challenge now is certainly to increase the sensitivity of the blood tests for this detection and to optimize the NGS approach, combining the search for EGFR; rearrangements in ALK, ROS1, RET, and NTKR, but also other genomic alterations such as BRAF, HER2, and MET; and investigations for MSI-H in LB. This requires mastering the pre-analytical phase as soon as the blood is sampled and the development of more sensitive technologies with a minimal amount of circulating DNA/RNA. Currently, other approaches are being studied for determination of the ALK status in urine or with plasma microRNAs . Finally, one of the major issues will be to propose robust and reproducible analytical tests to define the ALK status in blood, under the guise of quality control with accredited tests approved according to international norms .