Many direct and indirect methods have been developed to detect and characterize CTCs associated with lung cancer . These different methods have advantages and disadvantages . Different innovative technologies to improve the detection and characterization of CTCs in NSCLC have been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems . Direct approaches are based on the isolation of CTCs through their physical characteristics . Thus, in these latter methods, the CTCs are detected through their different size, their loss of deformability, their higher density and their electrical charges . Indirect techniques exploit the molecular properties of CTCs . Among these latter methods, the only FDA approved method for CTC detection, the CellSearch method (Janssen Diagnostics Company, Raritan, NJ, USA), has been FDA approved for CTC detection in metastatic breast, prostate and colon cancer patients. However, the CellSearch method has not been approved for CTC detection in metastatic lung cancer patients by the FDA. It is noteworthy that, since CTCs that have undergone epithelial-mesenchymal transition cannot express epithelial biomarkers, the CellSearch system can miss the detection of a number of CTCs of interest in lung cancer patients . Currently, the results obtained from CTCs characterization do not change the treatment of patients on a daily practice. Thus, to date, studies into the detection and characterization of CTCs are still a matter of translational and clinical research in NSCLC patients. The methods used to isolate free plasma DNA can also isolate circulating tumor DNA, which is present in variable amounts depending on the cancer patients and tumor stage. The volume of whole blood used is generally 10 mL but a larger volume is sometimes necessary for certain analyses, in particular NGS. The analyses are either targeted techniques such as allele specific PCR or droplet digital PCR or NGS techniques using panels of different genes. The sequenom mass array approach can also detect genomic alterations on several genes in blood samples . At present, the detection of activating or resistance mutations in EGFR in plasma samples can be performed in the clinical care of patients with advanced stage lung cancer according to the different practices available.