Uterine adenosarcoma is an extremely rare uterine malignancy, and the utility of chemotherapy in this disease is not well defined. This study assessed the safety and efficacy of trabectedin in patients with recurrent/metastatic uterine adenosarcoma with sarcomatous overgrowth. A retrospective search of a prospectively maintained database was performed to identify patients with adenosarcoma treated with trabectedin between 2010 and 2012, within a compassionate use trial. Three patients with recurrent/metastatic uterine adenosarcoma treated with trabectedin were identified. All three patients tolerated the drug well. Two patients obtained prolonged clinical benefit from treatment, one having received 17 cycles and another 11 cycles of therapy. Trabectedin is well tolerated and has clinical activity in recurrent/metastatic uterine adenosarcoma.