Background It was aimed to evaluate the relationship between delta neutrophil index (DNI) and neutrophil-tolymphocyte ratio (NLR) in the preoperative differentiation of nodular goiter and thyroid malignancy. Methods Patients over the age of 18 who underwent thyroid surgery between November 2014 and November 2019 were evaluated in this retrospective cohort study. Patients were divided into two groups according to their pathology results: malignant (Group M) and benign (Group B) thyroid disorders. White blood cell (WBC) count, neutrophil count, lymphocyte count, IG count and DNI were measured using an automated hematological analyzer from blood samples obtained at the preoperative period and postoperative 6th month of the follow-up. Neutrophil-to-lymphocyte ratio (NLR) values were manually calculated. Numerical data are expressed as means ± standard deviations (minimum-maximum values) or medians (minimum-maximum values) according to the normal distribution. Categorical values are expressed as percentages (%). Results A total of 243 patients (190 patients in Group B and 53 patients in Group M) who met the inclusion criteria were evaluated. The male/female ratio was 49/194. A statistically significant difference between Group M and Group B in terms of preoperative NLR, DNI and IG count was observed (p = 0.001, \ 0.001 and \ 0.001, respectively). No statistically significant difference was observed between the groups in terms of the control values performed in the postoperative period in terms of the NLR, DNI and IG count (p = 0.711, 0.333 and 0.714, respectively). A significant decrease was observed in the preoperative and postoperative DNIs, IG counts and NLRs in Group M (p = 0.009, \ 0.001 and \ 0.001, respectively). For the diagnosis of malignant thyroid diseases, the cut-off value of DNIs was C0.35%, and DNI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 79.2%, 78.9%, 79.2% and 77.9%, respectively (area under the curve [AUC]: 0.847; confidence interval [CI]: 0.784-0.911). The cut-off value of the IG count was C25/mm 3 , and its sensitivity, specificity, PPV and NPV were 83%, 72.1%, 83%, and 72.1%, respectively (AUC: 0.847; CI: 0.784-0.911). Conclusion DNI and IG counts are cheap and easily accessible tests that can be automatically calculated from automated systems without additional cost in differentiation of thyroid malignancies from benign disorders in the preoperative period.