BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center B-cell-like (GCB) and non-GCB subtypes. This study aimed to evaluate the immunohistochemical expression of CTLA-4 in these subtypes and its association with prognostic factors. METHODS: This retrospective study analyzed 50 cases of DLBCL. Clinical and histopathological data were collected, and CTLA-4 expression was assessed using immunohistochemistry. Statistical significance was determined using an unpaired t-test. RESULT: The average CTLA-4 expression in DLBCL was 50.46 cells per high-power field. Higher CTLA-4 expression was observed in the non-GCB subtype, patients younger than 60 years, females, those with stage III-IV disease, involvement of more than one extranodal site, and a low International Prognostic Index (IPI) score (0-2). A significant association was found between CTLA-4 expression and age (p = 0.045, 95% CI: 44.67-75.86). CONCLUSION: CTLA-4 expression was present in the tumor microenvironment of DLBCL. Higher expression was significantly associated with patients younger than 60 years.