The discovery of a nodule in the thyroid gland can be stressful for the patient, but 90% of nodules are clinically insignificant and benign. Fine needle aspiration cytology is the tool that can confirm the suspicious need for surgery. The established criteria for initial biopsy are based primarily on the size and ultrasound characteristics of the nodule. When the size is <1 cm, the first aspiration is not required unless the ultrasound shows suspicious features. Today, the natural course of thyroid nodules is unknown, and clinicians are unable to provide an evidence-based follow-up protocol for patients with nodules that are cytologically negative or not suspicious on ultrasound. The current recommendation is that repeat ultrasound and cytology be performed if progression is significant. The frequency and size of nodule growth has not been defined, and there is no reliable way to identify patients who are likely to progress. The hypothesis that nodule progression increases the chance of malignancy has also not been tested. In response to these unknowns, Dr. Durante et al. from Rome, Italy, conducted a prospective, multicenter, observational study, which ultimately showed that for inert and restrictive nodules, a safe follow-up protocol could be a second ultrasound examination 1 year after initial follow-up and re-evaluation after 5 years in the absence of progression. The literature was published in JAMA. The study included 992 consecutive cases based on 8 Italian thyroid centers between 2006 and 2008, and included patients with nodule characteristics: 1-4 asymptomatic, benign nodules on ultrasound or cytology. Follow-up was 5 years, ending in January 2013. The original observation endpoint was annual nodule growth, defined as significant growth as described above. Factors associated with nodule progression were determined using a multifactorial backward selection logistic regression model and RECPAM analysis. Secondary observational endpoints were new nodules and malignancy of primary nodules during ultrasound monitoring follow-up. Nodule growth occurred in 153 patients. After 5 years of follow-up, 174 (11%) of a total of 1567 primary nodes had increased in size by a mean of 4.9 cm, i.e., from 13.2 cm to 18.1 cm. factors associated with nodal growth included multiple nodes, primary node volume >0.2 ml, and males. Notably, nodule progression was less likely to occur above 60 years of age than below 45 years of age. Nodule shrinkage occurred in 184 (18.5%) patients. 5 patients (0.3%) progressed to cancer, of which 2 nodes did not increase in size. New nodules appeared in 93 (9.3%) patients, of whom 1 progressed to cancer. Current guidelines recommend repeat thyroid ultrasound every 6 to 18 months based on expert opinion and follow-up every 3 to 5 years if the nodule size is stable. For nodules with inert behavior and limited growth, in this study based on initial fine needle puncture or nodules less than 1 cm and non-suspicious ultrasound, a safe follow-up protocol is to perform a second ultrasound 1 year after the initial follow-up and evaluate after 5 years in the absence of progression. This follow-up strategy is appropriate for patients with a low rate of nodule progression in 85% of cases. Close follow-up is appropriate for younger patients or older obese individuals with multiple nodes or (and) larger nodes (>7.5 mm).