OBJECTIVES: Evaluate the cost-effectiveness analysis of erlotinib compared with docetaxel and pemetrexed in the second-line treatment of advanced non-small-cell-lung cancer (NSCLC) from a societal perspective in a Russian setting. METHODS: A Markov state transition model, based on two randomized phase III studies of erlotinib versus pemetrexed (HORTC) and pemetrexed versus docetaxel (Nasse H. et al 2005), was used to estimate total direct costs and quality-adjusted life years (QALYs). Data about cost of medical services and drugs are received from the price-list of out-patient medical aid in clinic MMA of I.M.Sechenov 01.02.2011, site minzdravsoc.ru//medicine and other accessible electronic resources. Costs, effectivenesses, utilities were discounted at 3%. Sensitivity analysis for key parameters in the model was conducted. RESULTS: Erlotinib was associated with a reduction in total costs (1 179 452 roubles versus 1 260 607 roubles and 1 769 367 roubles) and improved outcomes (total QALYs of 0.299 versus 0.248 and 0.271) in comparison with docetaxel and pemetrexed, respectively. Sensitivity analysis showed that major factors influencing cost-effectiveness and cost-utility ratios are survival gain, price of drugs, discount rates. CONCLUSIONS: In summary erlotinib is more cost-effective in comparison with docetaxel and pemetrexed for second-line treatment of advanced NSCLC due to lower adverse event and drug administration costs.