Whenever tissue sample is not available, non-small cell lung cancer (NSCLC) biomarker testing is performed with liquid biopsy. The Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is a novel target in patients with NSCLC. In this study, 33 NSCLC frozen plasma samples, previously characterised for KRAS mutational status by next generation sequencing (NGS), were processed by the fully automated Idylla KRAS assay. In 30/33 cases, archival matched cell-free DNA (cfDNA) was also directly pipetted in the cartridge. Overall, 30/33 plasma and 28/30 cfDNA samples yielded valid results. In 29/30 of KRAS p.G12C mutant plasma samples and 26/28 of cfDNA, Idylla confirmed the NGS results. In conclusion, the Idylla NSCLC KRAS liquid biopsy assay may represent a reliable tool to assess KRAS p.G12C mutation. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.