The most prevalent mutations in NSCLC involve intronic insertions within exon 20, with the Y772dupYVMA insertion accounting for 68% of all HER-2 exon 20 insertions, followed by G778dupGSP at 14% and G776delinsVC at 9%.62 HER-2 exon 20 insertions show an exclusion relationship with EGFR mutations and ALK rearrangements, and they are more prevalent in non-smokers, with a higher incidence in adenocarcinoma patients with brain metastases.63 For patients with metastatic LUSC, consideration should also be given to testing for HER-2 mutations. Here, EGFR is linked to adenocarcinoma.