Primary leiomyosarcomas (LMSs) of the lung are extremely rare malignancies that have been the subject of single or small series of case reports. Today, the gold standard of treatment in patients with locally advanced and metastatic disease includes one of the many possible regimens containing an anthracycline and/or ifosfamide. Few chemotherapy agents are active in the second-line setting. In particular, gemcitabine is considered quite ineffective in the treatment of first- as well as second-line chemotherapy of soft tissue sarcoma and responses to this agent are seldom reported. In this paper, we report a single patient with primary LMS of the lung previously treated with a combination of epirubicin and ifosfamide. The patient responded to second-line chemotherapy with gemcitabine 1250 mg/m2 given as a 30-minute infusion on days 1, 8, and 15 of a 28-day cycle and showed an 8-month response duration and negligible toxicity. Gemcitabine may represent an alternative to the best supportive care in patients affected with soft tissue sarcoma who fail first-line chemotherapy.