The BCL6 protein acts as a transcriptional repressor that is involved in the regulation of lymphoid development and function. Chromosomal rearrangements of the BCL6 gene region were found to occur in different types of non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The most common BCL6 translocation t(3;14)(q27;q32.3) results in the IGH-BCL6 gene fusion. In addition, more than 20 partner loci have been identified including immunoglobulin (Ig) genes but also a number of non-Ig genes. As a result of these translocations, the rearranged BCL6 gene comes under the control of the promoter of the partner gene leading to deregulated expression of BCL6. In DLBCL, the most common histologic subtype of NHL, BCL6 translocations represent one of the most frequent cytogenetic abnormality, occurring in 20% to 40% of the cases. Several studies reported a correlation of BCL6 translocation with an inferior overall survival. Moreover, DLBCL which are positive for both BCL6 and MYC rearrangements have been shown to have an extremely poor prognosis. Hence, the detection of BCL6 rearrangements by Fluorescence in situ Hybridization may help in predicting the clinical outcome in patients with NHL.