Recently, the frequency of lung adenocarcinoma has been increasing among nonsmokers, though the etiology remains unclear. Mutations of the epidermal growth factor receptor (EGFR) gene are frequently detected in the lung adenocarcinomas seen in nonsmokers. Thus, EGFR mutations can be implicated in carcinogenesis of lung adenocarcinoma. Herein, we report a case of 2 synchronous lung adenocarcinomas composed of 2 distinct pathological subtypes with different EGFR mutations: homozygous deletion in exon 19 in the papillary subtype of adenocarcinoma and a point mutation of L858R in exon 21 in the tubular adenocarcinoma. These findings suggest that specific mutations can occur randomly in the EGFR hot spot, and that these EGFR mutations can contribute to the distinct carcinogenic process of each adenocarcinoma.