BACKGROUND: Patients with plasma-cell neoplasia usually suffer from systemic disease, although a minority (< 5%) may present with solitary involvement of bone or soft tissue (extramedullary plasmacytoma (EMP)). Radiotherapy (RT) is a state-of-the-art treatment for these tumors offering long term curation. METHODS AND MATERIALS: Between January 2005 and January 2017, twenty-seven patients underwent RT at our institution. The aim of this study was to analyse the effectiveness of various RT doses for different forms of EMP. RESULTS: A total of 33 radiation courses were administered to 27 patients with a median age of 56 years. The median RT dose was 45 Gy (range: 12–55.8). The local control rate was 76% (93% for primary EMP vs. 61% for the secondary EMP lesions; P < 0.05). A complete response (CR) rate to local RT was achieved for 42% lesions (67% for primary EMP vs. 22% for the secondary EMP lesions; P < 0.01). The overall response rate (ORR) for the EMP lesions treated with high-dose regimens (> 45 Gy) versus low-dose regimens (≤ 45 Gy) was 87% versus 67%, respectively (P = 0.2). The median survival with high-dose RT group was significantly longer (P = 0.02). In subgroups analysis, primary EMP patients treated with high-dose RT had a non-significant higher ORR (100% vs. 80%, respectively; P = 0.3,) longer duration of LC (P = 0.3) with a longer survival (P = 0.05) than patients in low-dose group. No significant difference has been detected in secondary EMP patients treated with high-dose RT regarding ORR (60% vs. 62%, respectively; P = 1), and survival (P = 0.4). CONCLUSION: RT is an efficacious treatment modality in the treatment of EMP. A radiation dose ≤45 Gy confer acomparable CR rate to high-dose regimens and appears to be an effective treatment for controlling local EMP progression. Radiation dose-escalation may be beneficial for particular subgroups of patients.