Family history is an established risk factor for lung cancer. Previous studies have found that germline genetic alterations, such as those inEGFR,BRCA1,BRCA2,CHEK2,CDKN2A,HER2,MET,NBN,PARK2,RET,TERT,TP53, andYAP1, are associated with an increased risk of developing lung cancer. The study reports the first of a lung adenocarcinoma proband with germlineERCC2frameshift mutation c.1849dup (p. A617Gfs*32). Her family cancer history review demonstrated that her two healthy sisters, a brother with lung cancer, and three healthy cousins were positive forERCC2frameshift mutation, which might contribute to increased cancer risk. Our study highlights the necessity of performing comprehensive genomic profiling in discovering rare genetic alterations, early cancer screening, and monitoring for patients with family cancer history.