Purpose-Chloroma (granulocytic sarcoma) is a rare, extramedullary tumor of immature myeloid cells related to acute non-lymphocytic leukemia or myelodysplastic syndrome (MDS). Radiation therapy (RT) is often used in the treatment of chloromas; however, modern studies of RT are lacking. We reviewed our experience to analyze treatment response, disease control, and toxicity associated with RT in order to develop treatment algorithm recommendations for patients with chloroma.Materials/Methods-38 patients who underwent treatment for chloromas at our institution from 2/1990-6/2010 were identified and their medical records were reviewed and analyzed.Results-The majority of patients that presented with chloroma at the time of initial leukemia diagnosis (78%) have not received RT as it regressed after initial chemotherapy. Yet most patients that relapsed or remained with chloroma after chemotherapy are in the RT cohort (90%). 33 courses of RT were administered to 22 patients. Radiation sub-site breakdown was: 39% head and neck, 24% extremity, 9% spine, 9% brain, 6% genitourinary, 6% breast, 3% pelvis, and 3% genitourinary. Median dose was 20 (6-36) Gy. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) in the RT cohort were 39% and 43%, respectively at 5 years. At a median follow-up of 11 months since RT, only one patient developed progressive disease at the irradiated site and 4 patients developed chloromas at other sites. RT was well tolerated without significant acute or late effects, and provided symptom relief in 95% of cases. Conclusions-The majority of patients with chloromas were referred for RT when there was extramedullary progression, marrow relapse, or rapid symptom relief required. RT resulted in excellent local disease control and palliation of symptoms without significant toxicity. We recommend irradiating chloromas to at least 20 Gy, and propose 24 Gy in 12 fractions as an appropriate regimen.