A 28-year-old woman was admitted to our hospital with cough. CT scan indicated a huge mass in the anterior mediastinum. A transcutaneous needle biopsy showed tumor cell infiltration and compartmentalizing fibrosis. The tumor cells were positive for CD20 and CD45, and JH rearrangement was evident. The patient was diagnosed as mediastinal diffuse large-cell lymphoma with sclerosis. The tumor responded to combination chemotherapy. It should be emphasized that mediastinal diffuse large-cell lymphoma can be diagnosed using a small specimen obtained by transcutaneous needle biopsy.