<b><i>Background:</i></b> Involvement of the central nervous system (CNS) by mycosis fungoides (MF) is rare; however, it portends a poor prognosis. While aggressive multimodality therapy may improve outcomes, the role of radiation therapy (RT) is not well defined. <b><i>Objectives:</i></b> We sought to explore the efficacy of RT in the management of CNS involvement by MF. <b><i>Method:</i></b> We retrospectively identified five patients with MF and CNS involvement who received cranial or craniospinal RT at a single institution. Patient characteristics, disease features, radiographic findings, treatments delivered, and outcome data were extracted from the electronic medical record. <b><i>Results:</i></b> All 5 patients had neurologic deficits at RT initiation, and 4 experienced at least a partial improvement. Of 4 patients evaluated by MRI after RT completion, 3 had complete resolution of CNS disease within the irradiated field. At the time of last follow-up, all patients had died of MF. The median time to death was 7.4 months (range 1.0–21 months) from their diagnosis with CNS involvement and 1.2 months (range 0.4–7.1 months) from the end of RT treatment. <b><i>Conclusions:</i></b> We observed high rates of radiographic response and palliation of neurological symptoms. Nonetheless, all patients succumbed to their disease shortly after treatment, confirming the poor prognosis of this condition. Our findings suggest that RT may play a valuable palliative role for these patients.