The aim of this study was to evaluate retrospectively the response rate, progression-free survival and median duration of response to dacarbazine as second/third-line chemotherapy for refractory soft tissue sarcomas. We studied 40 valuable patients with refractory soft tissue sarcomas and confirmed progressive disease (median age 54 years; range 24-73) treated between May 1997 and October 2005: 30 (75%) with metastases, and 23 (57.5%) with grade 3 disease. Dacarbazine was given as second-line chemotherapy to 29 patients (72.5%) every 21 days using three different schedules: dacarbazine 800 mg/m2 on day 1 (26 patients); dacarbazine 400 mg/m2 on days 1 and 2 (five patients); and dacarbazine 300 mg/m2 on days 1, 2 and 3 (nine patients). There were no complete responses, three (7.5%) partial responses and five (12.5%) cases of stable disease, for an overall disease control rate of 20%. Median progression-free survival was 2 months and median response duration 9 months. The 3- and 6-month progression-free rates were, respectively, 25% (SE 6.85%) and 20% (SE 6.32%). There were no cases of grade 3-4 hematological and non-hematological toxicity. In conclusion, our results suggest that second/third-line therapy with dacarbazine leads to satisfactory disease control in refractory soft tissue sarcomas; its activity seems to be comparable with other treatments, such as high dose ifosfamide or ecteinascidin-743, but it has a better toxicity profile.