Primary extranodal lymphomas, a heterogeneous group of diseases of diverse etiology, pathogenesis, pattern of presentation and outcome, account for up to 20% of all malignant lymphomas. The gastrointestinal tract is the most common presenting site, but virtually every extranodal location has been reported. Most are B-cell, diffuse large-cell type; follicular histology is less common. In low-grade, particularly mucosa-associated lymphoid tissue lymphoma that tends be localized and is associated with an excellent prognosis, radiation therapy offers cure with minimal side effects. These include gastric, salivary gland, Waldeyer's ring and thyroid, orbital, low-grade lymphomas of the breast, and other less common sites. The intermediate-grade lesions of diffuse large-cell and B-lineage commonly occur in Waldeyer's ring, paranasal sinus, thyroid, breast, intestine, bone and are highly curable with combined modality therapy. Less common brain, testicular, ocular, T-cell tumors, including intestinal, nasal, and cutaneous lymphomas, currently evade cure and thus deserve special consideration. Many extranodal lymphomas are indolent and associated with a prolonged survival; knowledge of factors responsible for transformation to more aggressive forms of disease, ultimate dissemination, and potential curability of these disorders is limited. Accordingly, therapeutic trials focused on short-term outcomes are clearly of limited value for many of the indolent lymphomas. The future approach to management of extranodal lymphomas may have more basis in the etiology and pathogenesis of these disorders than purely on histological appearance and anatomic extent. Better understanding of the immune response and its relation to lymphoproliferative disorders may ultimately lead to a lesser focus on ablative cytotoxic therapies and an increased emphasis on specific etiological determinants and the control of aberrant immune response.