Background: DLCL with aberrations in MYC, BCL2 and/or BCL6 due to genetic alterations or protein expression is a high grade B-cell lymphomas with poor prognosis if received standard RCHOP chemotherapy. So that, different regimens are needed for better prognosis. Aim of the Study: Identify the association of protein, genetic expression of MYC, BCL2, and/or BCL-6 in cases of DLBCL, if MYC IHC could be used as a screening test to determine DHL or THL status, and to determine if the DHL or THL biology are related to any clinic-pathological features. Material and Methods: Thirty patients who were diagnosed with primary DLBCL from July 2015 to July 2018. The cases were collected from General surgery department-Faculty of medicine- Benha University and Assiut faculty of medicineAl-Azhar University were identified after applying exclusion and inclusion criteria. Clinico-pathological data was obtained by review of medical records and biopsy specimens for IHC and FISH were obtained from the Departments of general surgery. The FISH test (for MYC, BCL2, and BCL-6) and IHC (for CD10, KI 67, MYC, BCL2, and BCL-6) were performed. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 16 (p-value