A one-year-old, intact female, Maltese dog was presented with a history of anorexia and regurgitation. Thoracic radiographs and ultrasonography scans suggested an abnormal mass in the cranial mediastinal region, and computed tomography confirmed the origin of this mass. Ultrasound-guided fine needle aspiration cytology showed the presence of intermediate to large lymphoid cells showing mitotic figures. B-cell lymphoma was confirmed by the result of a polymerase chain reaction assay for antigen receptor rearrangement, therefore the patient was diagnosed with primary mediastinal large B-cell lymphoma (PMBL). The patient underwent L-CHOP (L-asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy, and showed complete tumoral remission from the beginning of chemotherapy. Seventytwo weeks after the completion of chemotherapy, the patient is still alive without any evidence of metastasis or relapse. A standardized treatment protocol has yet to be established for primary mediastinal lymphoma in dogs. This case report describes the complete remission of PMBL by an L-CHOP-based chemotherapy protocol in a young Maltese. Clinicians should consider that L-CHOP based chemotherapy may be useful against PMBL in dogs.