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Introduction Diffuse large B-cell lymphoma (DLBCL) accounts for 60% of lymphomas in India. Although the survival of DLBCL patients has improved following the addition of rituximab, a subset of patients do not respond well to therapy. Among the several factors responsible for this varied response, tumor microenvironment is considered to be crucial. This study is a search for such prognostic markers in the tumor microenvironment. Materials and Methods A total of 97 patients were selected, of whom 34 were treated with the CHOP regimen and 63 with RCHOP. Immunohistochemistry for CD68 was performed to study the stromal-1 signature and CD34 for stromal-2 signature. Results There was a significant increase in the counts of CD68-positive cells among patients free of events. CD34 count was higher in patients with events in both CHOP and RCHOP groups. Conclusion Additional assessment of stromal microenvironment along with the cell of origin might predict the clinical outcome better in DLBCL.