Efficacy of third-line chemotherapy treatment for small cell lung cancer (SCLC) is unknown. We present our experience with third-line chemotherapy for recurrent SCLC. Between January 1996 and July 2004 all consecutive patients treated for SCLC were retrospectively studied. We recorded patient characteristics, treatment details for each subsequent regimen, response to chemotherapy and survival. From 191 patients treated with chemotherapy 35 patients (18%) received third-line chemotherapy. At the start of third-line therapy, median age was 58 years (range 36-77), male/female 54%/46%, and ECOG performance score was 0/1/2/3 in 15%/64%/12%/9% of patients. Median time from diagnosis till start of third-line treatment was 15 months (range 5-34). Tumor response to first-line, second-line, and third-line therapy was 91%, 51%, and 26%, respectively. Median survival time estimated from the start of third-line treatment was 5 months (range 1-15). No toxic deaths were observed. Comparison of characteristics of patients who were treated with third-line chemotherapy with patients treated with maximally two lines of chemotherapy revealed that those who received third-line therapy were younger (p<0.001), had a better performance score (p<0.001), and had a better response to first-line treatment (p=0.004). In conclusion, third-line chemotherapy is still active in one in four SCLC patients.