© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Background: Atypia/follicular lesion of undetermined significance (AUS/FLUS) is still the most challenging category in the Bethesda System for Reporting Thyroid Cytopathology. Therefore, the aim of the current study was to investigate the value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in predicting malignancy in cases with AUS/FLUS nodules. Methods: A total of 200 patients with AUS/FLUS nodules who underwent thyroidectomy were included in this study. Preoperative hemogram parameters, ultrasonographic findings, fine-needle aspiration results, and postoperative final histopathological diagnoses of the patients were recorded retrospectively. Results: Thyroid malignancies were detected in 122 of the patients (61.0%). Patients in the benign group (BG) were older than those in the malignancy group (MG) (52.0 ± 11.3 vs. 45.9 ± 12.3 years, p < 0.001). The median TSH values of the two groups were comparable. Statistically significant differences were obtained between the two groups in respect of mean WBC of 7.53 ± 1.44 in MG and 6.87 ± 1.35 (103/mm3) in BG, mean neutrophil of 4.65 ± 1.12 in MG and 3.95 ± 0.99 (103/mm3) in BG, and median NLR of 2.18 (0.71–4.57) in MG and 1.75 (0.80–3.42) in BG (p < 0.001). The median PLR and MPV values of the two groups were similar. When NLR cut-off point was designated as 2.24, the accuracy of NLR in distinguishing malignancy from the benign condition was 0.65 in ROC analysis (area under the curve, 0.665; specificity, 0.808; sensitivity, 0.492). Conclusion: High NLR values may provide limited help in predicting thyroid malignancy in the AUS/FLUS nodule population, while PLR and MPV are not reliable parameters.