Purpose Retrospective study of effectiveness, toxicity, and relapse patterns after low-dose radiotherapy (LDRT) in patients with low-grade lymphomas. Methods 47 patients (median age 64 years) with 50 lesions were treated with LDRT (2x 2Gy). In 60%, LDRT was the primary and curative treatment, in 40% offered as second-line therapy in recurrent disease. Histology included follicular (57%) and marginal zone lymphomas (43%). Patients were followed-up regularly clinically (skin) and with CT or MRI scans. Results Median follow-up was 21 months. 84% of the lesions were extranodal disease (32% orbit, 14% salivary glands, 30% skin, and 8% others). Most lesions were similar to 5cm (90%) with a singular affection (74%). 26% of the patients received rituximab simultaneously. Overall response rate (ORR) was 90% (all lesions), 93.3% (primary treatment), and 85% (recurrence treatment); p=0.341. 2-year Local progression-free survival (LPFS) for all, curative, and palliative patients was 91.1%, 96.7%, and 83.8%, respectively; p=0.522. Five relapses were detected: three infield only, and were therefore treated with LDRT or subsequent local RT of 30Gy. Two patients showed an in-and outfield progression and were consequently treated with chemotherapy. Predictive factors for higher LPFS were tumor size similar to 5cm(p=0.003), similar to 2 previous treatments (p=0.027), no skin involvement (p=0.05), singular affection (p=0.075), and simultaneous rituximab application (p=0.148). LDRT was tolerated well, without detectable acute or long-term side effects. Conclusion Primary LDRT is an effective treatment with high ORR and long-lasting remissions in a subset of patients with low-grade lymphoma, and may therefore be a curative treatment option for patients with low tumor burden. LDRT with the CD20 antibody obinutuzumab will soon be tested in a prospective multicenter trial.