Indeterminate follicular thyroid lesions (Thyr 3A and 3B) account for 10% to 30% of all cytopathologic diagnoses, and their unpredictable behavior represents a hard clinical challenge. The possibility to preoperatively predict malignancy is largely advocated to establish a tailored surgery, preventing diagnostic thyroidectomy. We analyzed the role of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the lymphocyte-to-monocyte ratio (LMR) as prognostic factors of malignancy for indeterminate thyroid nodules. In patients affected by cytological Thyr 3A/3B nodules, NLR, PLR and LMR were retrospectively compared and correlated with definitive pathology malignancy, utilizing student’s t-test, ROC analysis and logistic regression. One-hundred and thirty-eight patients presented a Thyr 3A and 215 patients presented a Thyr 3B. After the logistic regression, in Thyr 3A, none of the variables were able to predict malignancy. In Thyr 3B, NLR prognosticated thyroid cancer with an AUC value of 0.685 (p < 0.0001) and a cut-off of 2.202. The NLR results were also similar when considering the overall cohort. The use of cytological risk stratification in addressing the management of indeterminate thyroid nodules in patients is not always reliable. NLR is an easy and reproducible inflammatory biomarker capable of improving the accuracy of preoperative prognostication of malignancy.