ObjectiveTo evaluate the diagnostic efficacy of thyroglobulin in fine-needle aspirate fluid (FNA-Tg) for detecting cervical lateral lymph node metastases (LLNM) in differentiated thyroid cancer (DTC). MethodsThe clinical data of DTC patients who underwent (selective) cervical lateral lymph node dissection at the 900th Hospital of the Joint Logistics Support Force from February 2021 to November 2023 were retrospectively analyzed. The significance level (α) was set at 0.05. ResultsAccording to the inclusion and exclusion criteria, a total of 155 patients with 179 lymph nodes were included, among which 49 lymph nodes were not metastatic and 130 were metastatic. The results of the integral analysis showed that the area under the receiver operating characteristic curve (AUC) of FNA-Tg for distinguishing cervical LLNM in the patients with DTC was superior to that of fine needle aspiration cytology (FNAC). The AUCs (95% confidence intervals) were [0.973 (0.950, 0.995) and 0.778 (0.708, 0.849), P<0.05], respectively, and the AUC (95% confidence interval) of the combination of the two was higher [0.978 (0.959, 0.997)]. The optimal diagnostic threshold of FNA-Tg was determined to be 16.45 μg/L or FNA-Tg/serum thyroglobulin >1. After stratification based on the size of the lymph nodes, a paired analysis of the two methods (FNA-Tg and FNAC) showed that the diagnostic efficiency of FNA-Tg was significantly higher than that of FNAC only when the short diameter of the lymph node was ≤0.8 cm (P<0.05), and its diagnostic efficiency was the best [0.955 (0.919, 0.992)], and there was no additional benefit from the combination of the two. ConclusionsThe results of this study suggest that FNA-Tg shows a good diagnostic efficacy for cervical LLNM in patients with DTC, especially has an obvious advantage for small lymph nodes with a short-axis diameter of lymph node ≤0.8 cm. Its optimal diagnostic threshold is 16.45 μg/L or FNA-Tg/serum thyroglobulin >1.