According to the latest guidelines, in patients with high-risk nodules with indeterminate cytology, diagnostic lobectomy should be the preferable surgical approach in the absence of factors that suggest a total thyroidectomy. This retrospective observational study has as its main aim the evaluation of the cases that underwent surgery, for Bethesda class IV nodules in our iodocarent geographical area. Particular attention was paid to carcinoma incidence, preoperative nodule size, histological characteristics of the neoplasm, surgical approach and eventual need of radiometabolic treatment. A total of 320 patients were included that underwent surgery for Bethesda IV nodules, between January 2010 and December 2020, at the General Surgical Clinic of the University Hospital of Parma, Italy. A total of 230 total thyroidectomies (71.9%) and 90 lobectomies (28.1%) were performed. Our data showed a strong impact of the 2015 ATA Guidelines on the surgical approach choice, with a progressive propensity towards a conservative approach and an increase of lobectomies from 7.2% to 41.5% after the new guidelines introduction. However, in our sample the percentage of lobectomies remains below 50%; this data is certainly influenced by the number of cases of multinodular pathology, often bilateral, in our geographical area. The nodules malignancy rate resulted 28.8%. Our data showed that increasing size correlated with an increasing malignancy rate (P<0.01), and follicular carcinomas were found to be larger than papillary carcinomas (P<0.001). A statistically significant correlation also emerged between nodule size increase and local/lymphovascular invasion (P<0.05). On the other hand, there was no statistically significant correlation between nodule size and multifocality, and between nodule size and presence of lymph node metastases. Out of the patients where it was possible to find this data, 66% underwent radioiodiometabolic treatment: 59% with papillary carcinoma, and 85% with follicular carcinoma. In patients with Bethesda IV thyroid nodules, diagnostic lobectomy should be the preferable surgical approach in absence of factors that suggest total thyroidectomy. In our opinion, total thyroidectomy remains the first choice in large nodules (≥4 cm) as these nodules have a high malignancy rate, greater local/lymphovascular invasion and a consequent frequent indication for post-operative radiometabolic treatment.