CD4 is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages and dendritic cells. It is a co-receptor that assists the T-cell receptor (TCR) with an antigen-presenting cell and also interacts directly with MHC class _ molecules on the surface of the antigen-presenting cells using its extracellular domain. In lymphatic tissues, the CD4+ T cells are seen in large numbers in the parafollicular zone, while scattered cells are found in the germinal centres and mantle zone. CD4 is also demonstrated in hepatic sinusoidal cells, monocytes and monocytes-derived cells but not expressed on B cells and immature thymocytes. Precursor T-lymphoblastic lymphomas are therefore variable in their expression of CD4. Most mature T-cell lymphomas are CD4 positive with the exception of aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma. CD4 plays an important role in the classification of lymphocytes in inflammatory lesions and malignant lymphomas.