Background: Diffuse large B-cell lymphomas of the central nervous system (DLBCL CNS) represent less than 1% of all lymphomas and between 2% and 3% of all cerebral tumors. They occur in adults of 60 years of age or more. The objective of this work is to describe the clinical-pathological characteristics, the immunophenotype and the differential diagnosis. Clinical Case: From the files of the surgical pathology unit we found four cases of primary diffuse large B cell lymphoma of the central nervous system in a 6-year period. Three corresponded to women over 47 years of age and the other to a 42-year-old man. The time of evolution was between 2 and 4 months. The symptoms were headache, blurred vision, hemiparesis, and seizures. Localization was in the pineal region, the frontal, parietal regions, and the right thalamus. Morphologically, large lymphoid cells with a diffuse growth pattern and necrosis were observed. Immunohistochemical markers, such as CD 20 and bcl2 were positive, one was positive to CD3. Expression of bcl6 and CD 10 was positive in one case, and MUM-1 was positive in three cases. All the cases were negative for Epstein-Barr virus. Conclusions: The diffuse large-B cell lymphoma of the central nervous system is rare. Its average age of presentation is at 60 years or older. The localization is in the pineal, frontal, parietal and thalamic regions. Three cases were originated by activated B lymphocyte (MUM-1 expression) and other from the Germinal Center (GC) (CD 10 expression). The clinical course was bad. The four patients died shortly after the diagnosis.