A patient with relapsed B cell non-Hodgkin lymphoma (NHL) infiltrating the Central nervous system (CNS) and resistant to chemotherapy was treated with intrathecal Rituximab (IT RTX), administered weekly for eight weeks at increasing doses, from 10 to 40 mg. After the second administration the patient showed significant clinical improvement and Cerebro spinal fluid (CSF) clearance of lymphomatous cells. A MRI scan performed after 30 days from the start of therapy showed full regression of lymphomatous infiltration. This report confirms the efficacy and safety of IT RTX in the treatment of CNS B-cell NHL.