Objective: Primary central nervous system lymphoma (PCNSL) is a specific type of non-Hodgkin lymphoma with poor prognosis. The rare incidence of this disease and difficulty to obtain sufficient tissue material impede deep research into PCNSL. However, application of modern molecular techniques makes it possible to find biological characteristics exclusive to PCNSL. Therefore, we systematically reviewed the latest research progress on biological characteristics and pathogenesis of PCNSL. Data Sources: The data analyzed in this review were from the articles listed in PubMed database. Study Selection: Articles focusing on the biology of PCNSL at the cytogenetic or molecular level were reviewed, including clinical, basic research, and review articles. Results: With respect to histopathology, perivascular growth pattern and reactive perivascular T-cell infiltration are regarded as typical histopathological manifestations of tumor cells in PCNSL. Moreover, tumor cells of PCNSL predominantly express an activated B-cell-like phenotype, including CD10 BCL-6(+) MUM1(+), CD10 BCL-6 MUM1(+), and CD10 BCL-6 MUM1. On the molecular level, some molecular and genetic alterations may contribute to malignant transformation, including mutations of proto-oncogenes and tumor suppressor genes, gains and losses of genetic material, as well as aberrant activation of some important signaling pathways, such as nuclear factor-kappa B and JAK/STAT pathway. Conclusions: The integrated molecular mechanisms involved in pathogenesis of PCNSL are not well understood. The important biomarkers indicating prognosis are not identified. Multicenter studies should be carried out to elucidate pathogenesis of PCNSL to find novel and effective therapeutic strategies.