Liposarcoma is one of the most common soft tissue sarcomas and has a number of different subtypes: well-differentiated; dedifferentiated; myxoid/round cell; and pleomorphic. However, the response of these subgroups to chemotherapy is not well documented. In this study, we have conducted a retrospective analysis of a prospectively maintained database of soft tissue sarcoma patients treated at the Royal Marsden Hospital. Eighty-eight liposarcoma patients who received chemotherapy between August 1989 and June 2004 were identified. The response rates to chemotherapy of the different histological subtypes and overall and progression free survival were investigated. Survival according to histological grade was also assessed. A statistically significant higher response rate to first-line chemotherapy was observed in patients with myxoid liposarcoma compared to de- and well-differentiated tumours, 48% (95%CI; 28-69) and 11% (95%CI; 2-29), P = 0.005. Similarly, those with myxoid liposarcoma had a significantly higher response rate compared to all other liposarcoma patients, 48% (95%CI; 28-69) and 18% (95%CI; 8-31). Patients with lower grade tumours had better overall survival. This retrospective analysis suggests that myxoid liposarcoma is relatively chemosensitive in comparison to a combination of other liposarcomas, and in particular de- and well-differentiated tumours. Further confirmation of these results should be sought by similar analyses of other databases.