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Patients with Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphomas (FL) exhibit marked variability in survival, the international prognostic index (IPI) predicts the cure with chemotherapy as IPI is a well established predictor of outcome in DLBCL and FL. Biological prognostic markers including expression on of BCL2, BCL6, CD5, CD10, and HLA-DR have been described as IPI independent prognostic factors. The purpose of this study is to high light how these biomarkers might be incorporated into current risk – adjustment models for prognosis. Biological parameters were evaluated by flowcytometric immunophenotyping of 96 patients with DLBCL and FL. In our study, Superior overall survival (OS) was associated with high expression of HLA-DR in DLBCL either do novo or on top of FL (p < 0.001 for both group), and with low expression of CD 5 and BCL2 in de novo DLBCL (p < 0.001 for both ) independently of the IPI. On the other hand Inferior overall survival was established with high expression of BCL6 in DLBCL. However Inferior progression free survival (PFS) was independently correlated with high expression of BCL2 (p = 0.007 and 0.018 ) and lower expression of HLA-DR ( p=0.003 and 0.03 ) in both de novo DLBCL and on top of follicular, but not in FL and with high expression of CD10 in de novo DLBCL only ( p In 96 patients with DLBCL and FL treated with risk adapted therapy, low HLA-DR expression is associated with poor outcome in DLBCL either de novo or on top of follicular but not in a FL group. the time is right to begin to consider how these biomarkers should be incorporated into current prognostic models to move beyond the clinically based IPI.