The advent of highly active antiretroviral therapy (HAART) has led to longer survival for patients with human immunodeficiency virus (HIV)-1 infection. As a result, nonacquired immune deficiency syndrome (AIDS)-defining carcinoma, mainly lung cancer, is becoming more prevalent among this population. A 62-year-old man with HIV-1 infection being treated with HAART was diagnosed with advanced lung adenocarcinoma harboring wild-type epidermal growth factor receptor with brain metastasis. He has been treated with seven lines of chemotherapy and radiotherapy to his brain with good control of the brain lesions. After more than 38 months, this patient remains alive with ongoing HAART therapy. Although advanced non-small cell lung cancer patients with concomitant HIV-1 infection are associated with poor prognoses, appropriate therapy may achieve outcomes similar to those seen in HIV-negative patients with advanced non-small cell lung cancer.