To investigate if these or related mechanisms may play a role in cetuximab resistance of HNSCC as well, we set out to scan the cetuximab-interacting ectodomain of the EGFR as well as KRAS/NRAS exons 2/3/4 and HRAS exons 2/3 for mutations in a cohort of 46 HNSCC patients by targeted next generation sequencing, 20 of these with available post-cetuximab circulating tumor DNA (ctDNA). This evidence concerns the gene KRAS and head and neck squamous cell carcinoma.