Blastic natural killer (NK) cell lymphoma/leukemia is a relatively rare NK cell malignancy. We report the second case of blastic NK cell lymphoma arising from the mediastinum with an aggressive clinical course. The patient was a 63-year-old Japanese man with an anterior mediastinum tumor. The biopsy specimen showed diffuse proliferation of tumor cells with frequent mitotic figures and apoptotic bodies. Both angiocentric features and small foci of coagulative necrosis were found in this section. The tumor cells had medium to large nuclei with a fine chromatin pattern, inconspicuous nucleoli and scanty cytoplasm. The nuclear contour was oval to moderately irregular, showing slight pleomorphism as compared with typical lymphoblastic lymphoma. The tumor cells were positive for CD2, CD56 and terminal deoxynucleotidyl transferase, but negative for other T-cell antigens, B-cell antigens and myeloid markers. In situ hybridization for Epstein–Barr virus encoded small ribonucleic acid 1 was negative.