Background: Uterine adenosarcoma is the rarest uterine sarcoma, with an age-adjusted incidence of 0.2 per 100,000 in the US population. Standard treatment involves surgical resection with hysterectomy and BSO, resulting in a 50-70% 5-yr overall survival (OS). Data regarding the responsiveness of this rare sarcoma subtype to standard sarcoma chemotherapy is lacking. The objective of this study was to review the MD Anderson experience in the treatment of this rare sarcoma specifically focusing on response to cytotoxic chemotherapy. Methods: Patients with uterine adenosarcoma seen in consultation between 1977 and 2014 were identified from the MDACC tumor registry. Clinical data was collected retrospectively. We used the Kaplan-Meier method to estimate OS and progression free survival (PFS). Response was determined using RECIST 1.1 criteria. Results: 157 Adenosarcoma Pts, with a mean age of 52 yrs, were identified. 60 developed local recurrence, 5 developed metastatic disease, and 10 developed both. Median OS for those Pts that developed locally recurrent and/or metastatic disease was 5.5 yrs. 58 of these Pts received at least one line of chemotherapy and constituted the study population. OS and PFS from 1^st line chemotherapy for those Pts was16 mo and 7.6 mo, respectively. Response rate (complete + partial response) and stable disease per RECIST for 1^st line chemotherapy were 40.0% (4/10) and 50% (5/10) for doxorubicin (dox) based regimens and 25% (2/8) and 37.5% (3/8) for gemcitabine/docetaxel (G/D). Median PFS for 1^st line chemotherapy dox based regimens was 5.4 mo, for G/D was 15.7 mo. Median OS for 1^stline chemotherapy dox based regimens was 12.9 mo, for G/D 24.9 mo. Potential confounders in this study, leading to these discordant results, are treatment with concurrent surgery or hormonal therapies. Conclusions: Adenosarcomas possess both epithelial and mesenchymal components and seem to respond less to G/D compared to dox based regimens. However, PFS is higher with G/D. If goal of therapy is to produce reduction in size of the tumor prior to surgery, dox based chemotherapy may have advantages. In the treatment of metastatic or unresectable disease where preservation of quality of life is needed, G/D may be the optimal choice.