Fine-needle-aspiration-cytology (FNAC) is safe and cost-effective procedure for evaluating thyroid nodules. The non-negligible rate of indeterminate thyroid nodule (ITN) cytology warrants diagnostic surgery for histological assessment, in some cases. Two recent studies (from Europe and the United States) reported that the clinical behavior of a histologically proven thyroid cancer (TC) varies according to its presurgical FNAC results. Despite differences in study design, inclusion criteria, and the use of different cytology classification systems (Italian and Bethesda), the overall results were comparable. In order to further discuss these results and to provide additional perspective on the topic, the senior authors of the 2 studies invited other thyroid experts and cytologists not involved in the previous studies to participate in the present commentary. The strong, consistent clinical message that emerges, especially regarding PTC, is that TC with an initial diagnosis of ITN has a less aggressive clinical presentation, lower rates of (1) lymph node metastasis
(2) more aggressive variants
and (3) BRAFV600E mutations compared with differentiated thyroid cancer (DTC) with an initial diagnosis of "suspicious for malignancy" or "malignant." These results were consistent in both studies and strongly point toward a more indolent clinical phenotype of DTC with a preoperative diagnosis of ITN as opposed to suspicious for malignancy or malignant. Further understanding the clinical implications of these data appears of clinical relevance and will be discussed from both the endocrinologist and the cytologist point of view. The here overviewed data provide the foundation for beginning to examine the impact of less aggressive therapies for TC with an initial ITN diagnosis.