•A woman with lung adenocarcinoma was found to carry a rare germline epidermal growth factor receptor (EGFR) variant, known as c.2527G > A, p.V843I.•The patient’s sister and mother also had lung cancer, but with only the mother carried the same EGFR p.V843I variant.•This appears to be the second reported case of familial lung cancer occurring in the context of a p.V843I germline variant.•p.V843I may be accompanied by other somatically acquired pathogenic variants in EGFR, usually in cis with the germline variant.•p.V843I is currently classified as a variant of unknown significance on ClinVar.•Reports of familial lung cancer can help with ultimate reclassification of p.V843I.•A proposed algorithm for germline variant testing in lung cancer is presented. Somatic epidermal growth factor receptor (EGFR) pathogenic variants have been identified and are routinely tested in the molecular diagnosis of non-small cell lung cancer (NSCLC) as they represent a target for EGFR tyrosine kinase inhibitor (TKI) therapy. However, germline variants in EGFR are much less frequently reported. Herein, we report the case of a 46-year-old woman diagnosed with lung adenocarcinoma who was found to harbor a rare germline missense variant in exon 21 of EGFR: NM_005228.5(EGFR):c.2527G>A (p.V843I). In the tumor, this variant (Cosmic ID COSV51767379) was accompanied by a secondary, known pathogenic EGFR variant in cis, also occurring in exon 21, c.2573T>G (p.L858R) (Cosmic ID 6224). Her mother was previously diagnosed with poorly differentiated lung carcinoma and her tumor was also found to harbour the p.V843I variant but no other pathogenic variants. Notably, the proband’s sister, diagnosed with a lung carcinoma with sarcomatous features at age 44, did not carry this variant or any other somatic or germline EGFR variants. This is the second report of familial lung adenocarcinoma associated with the germline p.V843I variant, which remains classified as a variant of uncertain significance. The lack of segregation of this variant in the proband’s affected sister illustrates the complexity with evaluating lung cancer predisposition factors. Currently, there is a paucity of data regarding the therapeutic outcomes of patients with tumors expressing this rare germline variant, therefore we propose an algorithm for the identification of at-risk individuals and families as the first step for their personalized management.