Background: Trabectedin (T) has shown objective response and disease stabilisation in 5%–10% and 30-40% of unselected patients with advanced soft tissue sarcoma (STS) failing prior anthracyclines and/or ifosfamide chemotherapy. Although the precise mechanism of action of T is not elucidated, this drug has been found to be more active in tumor cells with a deficient homologous recombination (HR) repair system. BRCA1 is a key player of the HER system. Our aim was to determine whether the BRCA1 single nucleotide polymorphims status was associated with clinical activity of T in advanced STS patients. Methods: We have analyzed single nucleotide polymorphisms of BRCA1 in a cohort of 135 patients with advanced STS from nine major referral European centres for STS. All patients were treated between 1999 and 2011 in phase I-II clinical trials or in the context of a compassionate-use programme. T was given at different doses (0.5-3 mg/m²) with the use of two different schedules: a 3-h infusion or a 24-h continuous infusion. BRCA1 haplotype was also assessed in two independent cohorts of patients: (i) localized STS (n=85); (ii) advanced STS managed with doxorubicin (n=44). Results: 734 cycles of T were administered, with a median of 3 cycles per patient (range 1–23). One complete response, 16 partial responses, and 29 disease stabilizations that lasted for >6 months were observed. The 6-months non-progression rate was 40.5% for patients who had at least 1 allele of the most frequent BRCA1 AAAG haplotype vs 16.5% for patients with a different haplotype; P = .01). This was also associated with a significant difference in terms of overall survival (P = .009). BRCA1 haplotype was not associated with outcome in the two independents cohorts of patients with localized STS or advanced STS treated with doxorubicin. Conclusions: BRCA1 haplotype may represent a predictive DNA-based biomarker for T efficacy in advanced STS patients. In particular, sarcoma patients without AAAG allele (26.5% of patients in our study) are not likely to have sustained benefit from T. Such a biomarker assessable form paraffin-embedded tumor material could be easily integrable into routine practice provided it is validated in a prospective setting.