[eng] Objectives: The main objectives of the study were 1) to set-up a droplet digital PCR (ddPCR) assay 25 for the non-invasive detection of G719S EGFR mutation in NSCLC patients; 2) to determine the 26 limits of detection of the ddPCR assay for G719S mutation and 3) to compare COBAS® and ddPCR 27 System for G719S quantification in plasma. Materials and methods: Blood samples were collected from 19 patients diagnosed with clinical 29 stage IVA or IVB NSCLC according to the TNM Classification of Malignant Tumors. Then, plasma 30 ctDNA was extracted with the Qiagen Circulating Nucleic Acids kit and quantified by QuantiFluor® 31 dsDNA System. The mutational study of EGFR was carried out by digital droplet PCR (ddPCR) with 32 the QX200 Droplet Digital PCR System with specific probes and primers. Results: We observed the lowest percentage of G719S mutant allele could be detected in a wildtype 34 background was 0,058%. In the specificity analysis, low levels of G719S mutation were detected in 35 healthy volunteers with a peak of 21.65 mutant copies per millilitre of plasma and 6.35 MAFs. In 36 those patients whose tissue biopsy was positive for G719S mutation, mutant alleles could also be 37 detected in plasma using both ddPCR and COBAS® System. Finally, when mutational status was 38 studied using both genotyping techniques, higher mutant copies/ml and higher mutant allele fraction 39 (MAF) correlated with higher Semiquantitative Index obtained by COBAS®. Conclusions: Although tissue biopsies cannot be replaced due to the large amount of information 41 they provide regarding tumor type and structure, liquid biopsy and ddPCR represents a new 42 promising strategy for genetic analysis of tumors from plasma samples. In the present study, G719S 43 mutation was detected in a highly sensitive manner, allowing its monitorization with a non-invasive 44 technique.