Background: Thyroid nodules are one of the most common diseases encountered in surgical practice. Predicting malignancy in patients with multinodular goiters (MNGs) becomes difficult due to the presence of multiple nodules. Targeting the nodule which might be malignant is of utmost importance. The task becomes difficult due to the presence of many different ultrasound scoring systems. This study aims to evaluate ultrasound characteristics and thyroid stimulating hormone (TSH) levels in predicting malignancy in patients with benign goiters and follicular neoplasia. Materials and methods: Our study was a prospective observational study that was conducted between April 2021 and September 2022. Patients aged 18 years and above with fine needle aspiration cytology (FNAC) suggestive of MNGs and follicular neoplasia were included in the study. Analysis of the variables was done by using statistical analysis in a social science application. Results: The final analysis was conducted on 106 patients who met the inclusion criteria. Ultrasound of the thyroid detected microcalcifications in 8.5% of patients, hypervascularity in 33%, solid components in 40.6%, and hypoechoic areas in 47.2% of the patients. The study showed that a TSH value of greater than 1.88 mIU/mL and solid components in ultrasonograph (USG) have high sensitivity and specificity in predicting malignancy. Conclusion: This study shows that ultrasound characteristics of microcalcifications, hypervascularity, solid component, and TSH level greater than 1.88 mIU/mL are statistically significant and can be fairly used for predicting malignancy in benign goiter and follicular neoplasia. The presence of these features may warrant a surgical excision to confirm the diagnosis, even if the FNAC is reported as benign.