In recent years, the spread of more-sensitive diagnostic methods has resulted in an increase of synchronous multiple primary lung cancer diagnosis. Nevertheless, its occurrence is still rare. Distinction between synchronous lesions from second independent primary tumors is a problem when dealing with multiple lung tumors, particularly if the histological type is the same. We present a case report of a 78-year-old female patient referred to our institution due to pneumonia. A subsequent thoracic computed tomography (CT) was performed showing two suspicious lesions, one in the right upper lobe and the other in the right inferior lobe. The CT-guided transthoracic needle biopsy of both pulmonary lesions revealed two adenocarcinomas, but with a rare combination of distinct morphologic variants, as well as different immunophenotypes and epidermal growth factor receptor (EGFR) gene status. The patient refused surgery and was submitted to stereotactic body radiation therapy (SBRT). She maintained tight follow-up and until now, she has not shown any signs of relapse or metastasis. A multidisciplinary approach with clinical, morphologic and molecular evaluation in multiple lung cancer is important to diagnosis and treatment guidance.