The World Health Organization classification of hematolymphoid tumors recognizes different specific lymphoma subtypes comprised of mature large B cells; however, many cases are still diagnosed as diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS). This entity is considered the most common non-Hodgkin lymphoma subtype, more often affecting older males in their sixth to seventh decades of life and the lymph nodes are the most affected structures, although up to 40% of the cases arise in extranodal sites. In the oral cavity, the gingiva and the palate are the most affected locations, more commonly manifesting as aggressive, rapidly growing swellings that may be asymptomatic or painful. Tumors are usually ulcerated and most cases have areas of necrosis. Radiographically, DLBCL NOS exhibits irregular, ill-defined radiolucent images. In the presence of EBV the tumor should be reclassified as diffuse large B-cell lymphoma EBV positive not otherwise specified (DLBCL EBV+ NOS), which is frequently associated with a poorer prognosis. Microscopically, the tumor shows a diffuse growth pattern of large cells that are positive for mature B-cell markers and demonstrate a high Ki67 expression. Different factors may impact patients’ prognosis, but the use of rituximab improved patients’ survival rates.