Background: The reported response rate to chemotherapy (CT) in SFT is low both with anthracycline-based regimens ( ≤ 20%) and with trabectedin ( < 10%). DTIC can be active. We report on the combination of doxorubicin + DTIC in a retrospective case-series analysis of SFT patients (pts) treated within 3 Italian sarcoma referral centers. Methods: We singled out metastatic SFT pts treated with CT from February 2012 to December 2015 at Fondazione IRCCS Istituto Nazionale Tumori - Milan, University Campus Bio-Medico - Rome and University Hospital “P. Giaccone” - Palermo, reviewing those receiving doxorubicin + DTIC. Pathologic diagnosis on last available tumor sample was centrally reviewed, distinguishing typical, malignant (MSFT) and dedifferentiated (DSFT) subtypes. Pts were treated until unacceptable toxicity or progression. All pts who received at least 1 cycle of chemotherapy were considered. Response was assessed by RECIST. Results: 13 cases were retrospectively identified (male/female: 9/4; mean age: 53 years, range 31-71; front-line/further-line: 11/2; MSFT/DSFT: 8/5). All pts were evaluable for response. Treatment was stopped in 11 cases (disease progression: 6 - maximum tolerated dose: 3 - surgery of residual disease: 2), while 2 pts are still on therapy. The mean number of cycles was 5 (3-6). There was no unexpected toxicity. Best response by RECIST was partial response (PR) = 6 (46%) - stable disease (SD) = 2 (15%) - progressive disease (PD) = 5 (39%). At a median follow-up of 19.2 months, median PFS was 6.3 months (range 2-32), with 3 pts being progression-free at 12 months. PR was detected in 3/8 MSFT e 3/5 DSFT, with a median PFS of 6.3 and 9.8 months in MSFT and DSFT, respectively. Median OS was 18.7 months (range 3-33). Conclusions: This small retrospective series suggests that doxorubicin + DTIC can be active in SFT. A higher response rate was observed in DSFT in comparison to MSFT (and pts with MSFT may have had an unsampled aggressive evolution). A prospective Phase 2 study on doxorubicin + DITC vs trabectedin in advanced SFT is under evaluation.