The Bcl-6 protein (B-cell CLL/lymphoma 6, zinc finger protein 51) is a nuclear zinc finger transcription factor with an N-terminal POZ domain. Bcl-6 represses p53 transcription by binding 2 specific DNA sites within the p53 promoter region and accordingly, p53 expression is absent in germinal centre B-cells where Bcl-6 is highly expressed. Most notably, constitutive expression of Bcl-6 protects B-cell lines from apoptosis induced by DNA damage. Bcl-6 is mainly used in the classification of B-cell lymphomas. In malignant lymphomas, Bcl-6 protein is most commonly detected in germinal centre neoplasms including follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (40%), lymphocyte predominant Hodgkin lymphoma, and even in peripheral T-cell lymphoma with follicular localization (“follicular T cell lymphoma”). It is also found in CD30+ anaplastic large cell lymphoma. Bcl-6 expression is virtually absent in acute lymphatic leukaemia and mantle cell lymphoma. Normal tonsil is recommended as positive and negative tissue control. Virtually all the germinal centre B-cells must show a moderate to strong nuclear staining reaction, while an at least weak to moderate nuclear staining reaction must be seen in the majority of squamous epithelial cells. In the mantle zones and interfollicular areas only dispersed cells should display a positive nuclear staining reaction.