Purpose <p>Thyroid nodules affect up to 50% of adults, although only 7–15% are malignant. However, the role of macrocalcifications in malignancy remains unclear. This study reassesses the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) framework by evaluating how excluding macrocalcifications from the scoring system impacts unnecessary biopsies and missed malignancies.</p> Methods <p>This single-center retrospective study evaluated thyroid nodules using cytological evaluation by fine-needle aspiration biopsy (FNAB) between 2012 and 2019. The clinical and sonographic characteristics of the nodules with and without macrocalcifications were compared. Additionally, the ACR TI-RADS classification was modified by removing the points assigned for macrocalcifications to assess their impact on the biopsy recommendations.</p> Results <p>We analyzed 287 thyroid nodules from 264 patients (median age 58.6 years, IQR 47.9–68.3; 84.8% female). Macrocalcifications were present in 41 nodules (14.3%) from 37 patients (14.0%). The malignancy rate did not differ significantly between nodules with versus without macrocalcifications (12.2% vs. 16.7%, <i>P</i> = 0.056). Stratified by ACR TI-RADS categories, nodules without macrocalcifications had significantly higher malignancy rates (<i>P</i> &lt; 0.001). Multivariate analysis (adjusting for sex, age, nodule size, and TI-RADS categories) showed no association between macrocalcifications and malignant cytology (OR 0.949, 95% CI 0.836–1.078, <i>P</i> = 0.622). After removing macrocalcification points, the modified TI-RADS classification reduced FNAB indications by 5.6% (<i>n</i> = 16) without missing any malignancies.</p> Conclusions <p>Excluding macrocalcifications from ACR TI-RADS scoring could reduce unnecessary biopsies without missing malignant nodules.</p>