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Primary CNS and intraocular non-Hodgkin's lymphoma is currently mostly treated with systemic chemotherapy. After initially successful tumor regression, recurrence is common and usually treated with radiotherapy. However, after good primary therapeutic response, new tumor growth is frequently observed. Because of actinic complications, radiotherapy can be applied only once. For an intraocular recurrence of primary CNS and intraocular lymphoma, intravitreal chemotherapy (0.4 mg methotrexate and 0.4 mg dexamethasone weekly for 4 weeks and once a month thereafter) can be performed. A few weeks after initiation, regression of intraocular tumors and eventually improvement of vision can be achieved. Eyes remained free of recurrence up to 2 years after initiation of intravitreal injections. Intravitreal chemotherapy is an effective treatment for ocular recurrence of primary CNS and intraocular lymphoma after systemic chemotherapy and radiotherapy.