BACKGROUND: Fine needle cytology (FNC) of thyroid nodules is not always diagnostic. Most of FNCs undeterminated for malignancy belong to the cytological class of “follicular neoplasm/suspicious for follicular neoplasm” lesions (FN). In this group only 10-30% of cases are malignant and the most appropriate surgical management is still controversial. Here, this issue was addressed and the more reliable predictive criteria of malignancy were also evaluated. METHODS: We retrospectively evaluated 472 patients, surgically treated after a FN diagnosis in a tertiary care referral center. In patients affected by bilateral thyroid disease with a cytological diagnosis of FN, or when high-risk clinical features and familiarity for thyroid cancer were present, total thyroidectomy (TT) was performed. Conversely, hemithyroidectomy (HT) was preferred when the nodule was single and when the age was ≤ 45 years. Frozen section examination was not used, and if cancer was diagnosed by definitive pathology of the HT specimen, the remnant thyroid lobe was removed. Histological features, surgical complications, and long-term outcomes of the remnant lobe were reported. Clinical features predictivity was also evaluated. RESULTS: TT was performed in 154/472 pts (32.62%), while HT was carried out in 318/472 cases (67.37%). The overall malignancy rate (MR) was 18.85% (89/472 pts), respectively 16% (51/318pts) following HT, and 24.6% (38/154pts) following TT, with a statistically significant difference. Similarly, the rates of transient and definitive hypoparathyroidism and the mean hospital stay following TT were higher than after HT (and statistically significant). Age < 45years and female gender were more frequently associated to malignancy. The rate of complications following second surgery was comparable to that of primary HT. In the HT group incidence of unexpected contralateral papillary thyroid cancer (PTC) was 9.8% and, after 88.2 ± 30.42 months mean follow-up, completion surgery for benign pathology was carried out in 6.7% of cases. CONCLUSIONS: Our data show that histology following a cytological FN diagnosis is malignant only in a low percentage of cases (89/472, 18.85%). Following TT, a MR higher than in HT was observed. Even if some clinical features are cancer associated, malignancy cannot be reliably predicted before surgery. Thus, in solitary low-risk lesions, HT is still the standard of care. Its lower complication rates makes HT the safest procedure. In case of multiglandular disease TT may be recommended. Further investigation is warranted to achieve a better preoperative diagnostic accuracy in order to reduce the amount of surgical operations with diagnostic aim.