Abstract: The concept and understanding of central nervous system (CNS) lymphoma have greatly evolved in the past few years. Better characterization of a number of lymphoproliferative neoplasms through clinical, immunophenotyping, and molecular studies is reflected in a much more complex WHO Classification of Tumours of Hematopoietic and Lymphoid Tissue. The term “primary CNS lymphoma” is now restricted to primary diffuse large B-cell lymphoma confined to the CNS (and/or to the eye) that occurs in immunocompetent patients. Many other lymphoma subtypes, some of which are primary or exclusive to the CNS, such as lymphomas of the dura and immunodeficiency-associated lymphomas, are excluded from this definition. We describe the clinical and morphologic features of a diverse group of lymphomas occurring in the CNS, including primary CNS lymphoma, primary vitreoretinal lymphoma, lymphomatosis cerebri, Epstein-Barr virus–associated lymphoproliferative disorders, low-grade B-cell lymphoma, T-cell lymphoma, anaplastic large cell lymphoma, intravascular large B-cell lymphoma, and Hodgkin lymphoma. The purpose of this review is to provide a practical approach to the diagnosis of an often-challenging entity, focusing on how to maximize the use of small tissue biopsies and prevent diagnostic traps, which we have encountered with similar cases. Clinical, radiologic, and histologic examples are presented.