Leiomyosarcoma is a heterogeneous tumor group, representing <1% of all new cancers diagnosed in United States. Treatment choice is based upon site, grade, and extent of disease. However, prognosis for metastatic or unresectable sarcoma is very poor with reported median survival of 12 months. Response to chemotherapy has been approximately 8% to 39% based upon the chemotherapeutic agent and whether used alone or in combination. Vorinostat is an orally active, potent, and competitive inhibitor of histone deacetylases approved for cutaneous T-cell lymphoma. There are limited preclinical data illustrating the activity of histone deacetylase inhibitors in sarcoma. Here is a case of a lady with leiomyosarcoma who has progressed through multiple chemotherapeutic agent who has achieved a partial response to vorinostat treatment.