Abstract. Introduction: Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B-cell lymphoma for which no optimal treatment has been established and prognosis remains poor. Here, we describe a human immunodeficiency virus-uninfected patient with PBL that was refractory to conventional chemotherapies but was successfully controlled with a bortezomib-based regimen followed by a lenalidomide-based regimen. Case Presentation: A 64-year-old man suffered from nasal bleeding and occlusion. Whole-body computed tomography results revealed a large lesion occupying his nasal cavity. He was diagnosed with PBL based on a tumor biopsy and was treated with two lines of conventional chemotherapy. A dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) regimen and an ifosfamide, carboplatin, and etoposide (ICE) regimen were ineffective, but the bortezomib-based regimen CyBorD (bortezomib, cyclophosphamide orally, and dexamethasone orally) provided a clin