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Background Lymphoma is the most common blood cancer. Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL. In Egypt, It represents about 49% of NHL presenting to the National Cancer Institute (NCI), Cairo University. It is an aggressive lymphoma where multiple clinical and laboratory prognostic factors affect its clinical course. Aim The aim of the present study was to determine MYC protein score immunohistochemically and by using image optical density (IOD) in relation to secretor status in patients with DLBCL in order to extrapolate their clinical and prognostic impact. Method Thirty DLBCL patients were enrolled in this study during the period from Oct.1st, 2014 to Oct.1st, 2016 and 15 matched normal subjects as control. The follow up period for the patients was 24 months. A full medical history was taken together with laboratory analyses. Results According to our findings, a high significant relation was found between c-Myc score and IPI (p = 0.009). The mean IOD for Myc expression was statistically and significantly higher in patients with high IPI ((p = 0.001) at a cut off value of 50%) splenomegaly was higher among male patients, lymphocyte/monocyte ratio (LMR) was significantly lower in patients than in the control group and was associated with positive MYC protein expression with high scores (=50%). Our study also confirmed that secretor status (B +ve) Lewis blood group phenotype carried a better prognosis, a higher overall survival associated and a lower MYC protein score. MYC protein in our patients was significantally correlation to ß2M (r= 0.791), LDH (r= 0.697), IPI (r= 0.562) and IOD (r= 0.996). There was a significant negative correlation to Absolute Lymphocytic Count (ALC) (r= - 0.590) and LMR (r= - 0.694). Age, hemoglobin, TLC and platelet count did not show any significantt correlation to MYC protein. Conclusion Expression Determination of MYC scoring and secretor state are highly recommended at the initial evaluation of DLBCL patients. [ABSTRACT FROM AUTHOR]