The purpose of this study was to determine the activity of third-line chemotherapy for non small lung cancer (NSCLC). This retrospective study included patients who had failed after a second-line chemotherapy. A total of 16 patients treated with third line chemotherapy were evaluated. Only one patient had a partial response (6.2%), with an additional 4 patients (24.8%) with disease stabilisation. The median time to progression was 46 days and the median overall survival time was 132 days after the onset of third-line therapy. The overall survival (OAS) after the third-line chemotherapy was linked with the presence of objective response achieved by the first-line treatment (p=0.009). Likewise, the progression free survival (PFS) was related with the presence of clinical benefit (complete + partial response + stable disease) after the first-line chemotherapy (p=0.044). However, other factors evaluated as potential predictors of PFS, or OAS were not found to be of significance. As a conclusion; highly selected patients, who have objective response to the first-line therapy may be offered a third-line chemotherapy regimen, provided that they have a good performance status. [Turk J Cancer 2004;34(1):19- 23]