A 61-year-old woman developed an asymptomatic tumor on her right cheek. She had a history of surgical removal of a similar tumor on her left arm 2 years earlier. The facial lesions were flesh-colored, with 2×2 cm ulcers (Fig. 1). The left arm had ulcerative nodular lesions around the operation scar. Laboratory examinations revealed marked leukocytosis (19,510/μL) with lymphocytosis (54.6%). A few abnormal blastoid cells with large nuclei were detected by hemogram (Fig. 2). The red blood cell count, platelet count, coagulation tests, liver, and renal functions, including serum lysozyme, lipase, α1anti-trypsin, and angiotensin-converting enzyme activities, were normal, but a moderate elevation of thymidinekinase activity was observed. Anti-nuclear human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) antibodies were not detected. Mantoux reaction was negative and no DNA of tuberculosis was detected by polymerase chain reaction. Epstein–Barr virus (EBV) titers revealed EBV viral capsid antigen (VCA)-immunoglobulin G (IgG): ×160; VCA-IgM: undetectable level; early antigen (EA)-IgG: ×10; and EBNA: ×80. The lymphocytes showed normal proliferation responses to lectins. The tumor biopsy specimen revealed marked lymphocyte infiltration around vessels and focal necrosis in the deep dermis (Fig. 3a). The infiltrate was composed mainly of large blastoid lymphocytes with mitotic figures. Around the destroyed dermal vessels, tumor cells and denatured endothelial cells concentrated characteristically and formed glomeruloid lesions (Fig. 3b). Many auto-phagocytes forming “bean bag cells” were electron microscopically detected in the tumor. The proliferated cells in the dermis were CD3+, CD4+, CD7+, CD2+, CD5+, WT31+, and CD45RO+; however, CD1, CD8, TCRd1, CD16, CD56, CD57, CD19, CD20, CD10, L26, and LMP-1 were negative. Bone marrow cells showed lymphocytosis (39%) mixed with abnormal lymphoid cells. Rearrangement of T cell receptor (TCR)-β or TCR-γ chain was not detected in the samples from dermal tumors and peripheral blood. EBV-encoded small nuclear RNA (EBER) was detected in the tumor cells from the forearm by in situ hybridization. Thus, the patient was diagnosed as having EB virus-related angiocentric lymphoma with leukemic change, and was treated with bi-weekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) combination chemotherapy. The facial tumor responded to CHOP markedly, and the peripheral blood leukemic cell count declined after two cycles of CHOP. After the sixth cycle of CHOP, however, the patient developed acute interstitial pneumonitis, and died from an intracranial hemorrhage. The autopsy specimens revealed thickening of the alveolar wall, septal fibrosis, and alveolar epithelial necrosis with focal lymphocyte infiltration. The bone marrow was hypocellular, but infiltrated with blastoid tumor cells.