CNS recurrence of non-Hodgkin lymphoma is fetal in most cases and tends to occur 5–12 months after the initial diagnosis [1]. Risk factors for CNS involvement include advanced stage, increased IPI, raised LDH, young age, [1 extranodal site, B symptoms, low albumin and retroperitoneal disease. A 19-year-old Japanese man presented to our hospital because of persistent cough on October 2007. A CT scan showed an anterior mediastinal tumor of 8 cm in diameter. LDH value and bone marrow examination were normal. After the total resection, the tumor was diagnosed as primary mediastinal large B-cell lymphoma (PMLBL). Involvement of right infraclavicular lymph nodes detected by Ga-SPECT and FDG-PET/CT determined the stage as IIA. One cycle of MACOP-B regime plus bi-weekly rituximab therapy started on November 2007. After confirming complete response (CR) by CT and Ga-SPECT, 30 Gy of involved field irradiation to the mediastinum and bilateral infraclavicular lymph nodes followed. On June 2008, 3 months after the chemoand radio-therapy, FDG-PET/CT revealed diminishment of abnormal accumulation. On July 2008, only 4 months after the completion of treatment, severe headache and nausea started. A cranial MRI scan showed an enhancing mass in the left frontal lobe with the right midline shift (Fig. 1). Although systemic evaluation revealed no recurrence in the other sites, brain biopsy confirmed infiltration of the lymphoma cells. Southern blot analysis of JH region of immunoglobulin heavy chain gene showed identical rearrangement bands in mediastinal tumor and CNS metastatic mass. The result confirmed that the CNS tumor is truly derived from primary mediastinal mass. The CNS lesion was resistant to two cycles of IVAM therapy containing high-dose methotrexate (MTX) and the following whole brain irradiation of 50 Gy. Then, after obtaining informed consent from the patient, we introduced via Ommaya reservoir three times of 10–25 mg of rituximab together with 3 ml of the autologous serum twice a week. The intracranial rituximab therapy failed to reduce the tumor size at least until day 15, when the patient’s condition rapidly deteriorated and subsequently he died of bacterial pneumonia. PMLBL is a relatively rare subtype of diffuse large B-cell lymphoma (DLBL) and usually occurs in young patients. MACOP-B regimen plus rituximab (R-MACOP-B) combined with local mediastinal radiation ([30 Gy) is recommended as a front-line therapy for the PMLBL patients [2]. This approach has demonstrated a stable progression-free survival in about 70% of the patients 2 years after the diagnosis. The presented patient was also treated with R-MACOP-B combined with involved field radiation and had no CNS risk factors except for young age, but he relapsed only 4 months after the completion of treatment. CNS relapse is reported in more than 10% of NHL arising from the testis, breast and paranasal sinuses, and CNS prophylaxis is recommended to these subtypes of DLBCL [3, 4]. Bishop et al. reported that CNS infiltration occurs in 4% of newly diagnosed PMLBL cases and in 11% of relapsed ones [5]. Although CNS recurrence has been reported in 2–10% of PMLBL patients [6–8], only one report has referred the CNS screening and prophylaxis in PMLBL [3]. Stefoni et al. reported a case of PMLBL M. Sasaki (&) K. Sugimoto A. Masuda Y. Tsukune Y. Yahata N. Komatsu Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan e-mail: msasaki@juntendo.ac.jp