**Abstract**

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous class of aggressive lymphoma and is considered as the most common subtype of non-Hodgkin lymphomas (NHL). Several genetic anomalies such as point mutations, numerical alterations, and, more rarely, translocations and gene amplifications play a role in the pathogenesis of this class of B-cell lymphoma and have been related to specific histological and immunophenotypic subtypes. On the other hand, the treatment protocol in DLBCL did not witness significant changes during the last two decades. The widespread adoption of rituximab as an important adjuvant to standard chemotherapy protocol in CD20+ cases was a notable exception, which provided significant improvement in disease-free survival and overall survival, with limited toxicity. However, no less than 20% of patients diagnosed with DLBCL exhibit relapse after the initial response to R-CHOP regimen, while more than 15% of the patients exhibit primary refractory disease. This is the reason why a review of all the morphological, clinical, and therapeutic particularities of DLBCL is required.

**Keywords:** diffuse large B-cell lymphoma, immunohistochemistry, lymphoma, molecular diagnostics, rituximab-CHOP
