Background: Sonographic risk patterns identified in established risk stratification systems (RSS) may not accurately stratify follicular carcinoma from adenoma, which share many similar US characteristics. The purpose of this study is to investigate the performance of a multimodal machine learning model utilizing radiomics and topological data analysis (TDA) to predict malignancy in follicular thyroid neoplasms on ultrasound. Patients & Methods: This is a retrospective study of patients who underwent thyroidectomy with pathology confirmed follicular adenoma or carcinoma at a single academic medical center between 2010 and 2022. Features derived from radiomics and TDA were calculated from processed ultrasound images and high-dimensional features in each modality were projected onto their first two principal components. Logistic regression with L2 penalty was used to predict malignancy and performance was evaluated using leave-one-out cross-validation and area under the curve (AUC). Results: Patients with follicular adenomas (n 5 7) and follicular carcinomas (n 5 11) with available imaging were included. The best multimodal model achieved an AUC of 0.88 (95% CI: [0.85, 1]), whereas the best radiomics model achieved an AUC of 0.68 (95% CI: [0.61, 0.84]). Conclusions: We demonstrate that inclusion of topological features yields strong improvement over radiomics-based features alone in the prediction of follicular carcinoma on ultrasound. Despite low volume data, the TDA features explicitly capture shape information that likely augments performance of the multimodal machine learning model. This approach suggests that a quantitative based US RSS may contribute to the preoperative prediction of follicular carcinoma.  Kulcsszavak: topological data analysis, follicular carcinoma, multimodal, thyroid nodule, machine learning