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Aim: This study aimed to evaluate the diagnostic performance of the Delta Neutrophil Index (DNI) and Neutrophil-to-Lymphocyte Ratio (NLR) in distinguishing malignant from benign primary brain tumors during the preoperative period. Methods: This retrospective cohort study was conducted at a tertiary university hospital. A total of 140 participants were included 60 patients with malignant glial tumors, 50 patients with benign brain tumors, and 30 healthy controls without inflammatory, infectious, or hematologic disease. Preoperative complete blood count results obtained within seven days before surgery were analyzed. Results: Patients with malignant tumors were significantly older than those in the benign and control groups (p < 0.001). DNI, NLR, PLR, MLR, and SII values were all significantly elevated in the malignant group (p < 0.001, for all comparisons). ROC analysis revealed high diagnostic accuracy for DNI (AUC = 0.847) and NLR (AUC = 0.850), with optimal cut-off values of 3.50 and 3.95, respectively. In multivariable logistic regression adjusted for age, DNI > 3.5 (OR = 20.67; 95% CI: 3.35-127.64; p = 0.001), NLR > 3.95 (OR = 21.17; 95% CI: 3.28-136.50; p = 0.001), and CRP (OR = 1.52; 95% CI: 1.20-1.93; p = 0.001) remained independent predictors of malignancy. The combined model including DNI and NLR achieved the highest diagnostic accuracy (AUC = 0.937; age-adjusted AUC = 0.943), with a sensitivity of 88.3% and a specificity of 86.0% after age adjustment. Conclusions: Both DNI and NLR demonstrated significant value in differentiating malignant from benign primary brain tumors prior to surgery, with DNI emerging as the most powerful independent predictor. The combined use of DNI and NLR substantially improved diagnostic accuracy, suggesting that simple hematologic indices may serve as practical, noninvasive adjunctive tools in the preoperative assessment of brain tumor malignancy. These markers may assist in surgical prioritization, patient counseling, and clinical decision-making, particularly in resource-limited settings.