Epstein-Barr virus (EBV)-associated natural killer (NK)/T-cell lymphomas show a geographical predilection for Asian and South American populations and are rare in Western countries. They predominantly occur in extranodal sites, including the nasal or paranasal areas, and less frequently in the localized nodal lesion. Most of the tumor cells exhibit a cytotoxic phenotype, characterized primarily by the expression of granzyme B and perforin. EBV is usually detected in tumor cells by using EBV-encoded small RNA in situ hybridization (EBER), suggesting that EBV plays an important role in lymphomagenesis. In this chapter, we have described 2 diseases: 1) extranodal NK/T-cell lymphoma, nasal type (ENKL), representative of extranodal EBV-associated NK/T-cell lymphoma; and 2) nodal cytotoxic molecule-positive EBV-positive peripheral T-cell lymphoma, not specified type (CM + EBV + PTCL-N), representative of nodal lymphoma. Both ENKL and nodal CM + EBV + PTCL-N are intractable to standard chemotherapy. Although ENKL is sensitive to radiotherapy, it shows a poorer response to chemotherapeutic agents than other lymphomas because of P-glycoprotein expression. P-glycoprotein is a product of the multidrug resistance (MDR1) gene, which is a major cause of the refractoriness of malignant lymphomas to conventional chemotherapeutic regimens containing anthracycline. l-asparaginase-containing regimens such as SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) are effective for ENKL. Evaluation of effective chemotherapy for nodal CM + EBV + PTCL-N is ongoing.