Malignant lymphoma of diffuse large cell type, was diagnosed in a 70-year-old man with tumors of the nasal cavity and right testis. He was treated with Epi-VEPA regimen and relapsed in the right thalamus just after achieving remission. Total cranial irradiation was effective, but multiple skin lesions were present at the time. He then suffered from renal failure and delayed clearance of MTX after high-dose methotrexate (MTX) administration with citrovorum factor (CF). The serum concentration of MTX decreased to 0.09 microM within 285 hours by multi-clearance techniques as continuous arteriovenous hemoperfusion (CAVH), plasma exchange (PEX), peritoneal dialysis (PD) and charcoal hemoperfusion (CH). Better MTX clearance was observed in CH and PEX than in CAVH and PD, with higher effect in PEX than in CH or CAVH. The patient suffered severe mucositis and myelosuppression, but fatal harm of MTX was prevented. CH and PD were considered the best combination of clearance techniques for removing serum MTX in delayed methotrexate clearance with renal disturbance.