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Background: Diffuse large B cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma, characterized by remarkable molecular heterogeneity. This study evaluates the prevalence of MYC, BCL2, and BCL6 gene rearrangements among Iranian DLBCL patients. Method: This historical cohort study encompassed 152 patients drawn from six reference hospitals who participated in the research. Interphase dual-color break-apart fluorescence in situ hybridization (FISH) was applied to formalin-fixed paraffin-embedded DLBCL specimens categorized as "not otherwise specified" alongside 20 normal controls. Survival data was analyzed using the Kaplan-Meier method and the Log-Rank test. Results: Among the patients, 7 (4.8%), 4 (2.9%), and 15 (10.2%) exhibited MYC, BCL2, and BCL6 rearrangements, respectively. Additionally, 1.5% of the patients demonstrated double-hit (DH) characteristics with both MYC and BCL2 rearrangements, while no triple rearrangements were observed. The presence of rearrangements appeared to be independent of clinicopathological variables. Patients with rearrangements experienced reduced survival durations, with reductions of 26.6, 31.2, 9.1, and 34.2 months for MYC, BCL2, BCL6-rearranged, and DH tumors, respectively (P > 0.05). Adverse prognosis was associated with age, activated B-cell-like phenotype, disease stage, B symptoms, lactate dehydrogenase levels, and risk grouping according to the National Comprehensive Cancer Network (NCCN) International Prognostic Index. Conclusion: DLBCL cases featuring MYC, BCL2, and/or BCL6 translocations are relatively rare. Patients harboring these rearrangements tend to exhibit aggressive disease progression with shortened overall survival. However, these differences did not reach statistical significance, necessitating further research to validate the incorporation of such tests into the routine workup of DLBCL patients. [ABSTRACT FROM AUTHOR]