ERBB2 exon 20 insertions occur within exon 20, which encodes part of the kinase domain. These mutations occur with a frequency of approximately 2--4% of all NSCLC. Overall, in-frame ERRB2 insertions in exon 20 have been reported in approximately 6% of cases of lung adenocarcinoma which are negative for EGFR, KRAS, ALK alterations and these variants are more frequent in patients who were never-smokers. Mutations in ERRB2 do not have an independent prognostic value in lung adenocarcinoma, according to a recent study. In vitro studies have shown that this specific variant is associated with constitutive kinase activation and is associated with sensitivity to some ERBB2 inhibitors and therefore, it may represent a targetable mutation in some clinical settings. Please refer to clinicaltrials.gov for additional information. Recommend correlation with other clinical and laboratory findings.