A case of successful and prolonged treatment of metastatic non-small cell lung cancer with the epidermal growth factor receptor antagonist erlotinib is presented. A never-smoker female was diagnosed with stage IV lung cancer in December 2005. A chest CT scan showed soft tissue mass 35×34 mm in size in the right lung with metastases in the lymph nodes and in the left lung. A biopsy revealed a poorly differentiated adenocarcinoma. The disease showed poor response to the first-line and second-line chemotherapy. Targeted therapy with erlotinib was started in February 2007. The most severe adverse event observed was grade 3 skin rash. The disease was stable until February 2009 when brain metastases were detected. Erlotinib was continued until May 2009 when disease progression in the lungs was confirmed. The patient died due to ongoing disease progression in December 2009. Retrospective genetic analysis of a tumor specimen was performed, and no mutations in EGFR exons 18-21 were detected. The patient had a significant clinical benefit for the period of 24 months. These results are consistent with previous reports in literature that clinical characteristics such as female gender, nonsmoker, adenocarcinoma histology, and severe cutaneous toxicity seem to predict good response to erlotinib. In the present case, erlotinib proved to be effective even in heavily pretreated, chemotherapy-resistant lung adenocarcinoma. So far, no exact predictive biomarkers of erlotinib effectiveness have been determined; and their further analyses are essential.