Abstract:Ki-67, a key marker of cellular proliferation, has gained increasing recognition in the management of medullary thyroid carcinoma (MTC). With the establishment of the International Medullary Thyroid Carcinoma Grading System (IMTCGS), a Ki-67 proliferation index ≥5% has been incorporated as a major criterion for defining high-grade MTC and predicting adverse outcomes. This review provides a comprehensive overview of the role of Ki-67 across the continuum of MTC care. In diagnosis, the Ki-67 index assessed in fine-needle aspiration samples correlates well with surgical specimens and assists in predicting tumor grade and optimizing imaging strategies. In prognosis, elevated Ki-67 levels are significantly associated with aggressive clinicopathological features, shorter survival, and accelerated calcitonin/CEA doubling times, establishing Ki-67 as a robust independent prognostic indicator. In therapeutic decision-making, Ki-67 may help determine surgical extent, guide postoperative surveillance, and serve as a dynamic marker for evaluating response to targeted therapies. Ki-67 also demonstrates potential complementary value when combined with RET mutations and other molecular biomarkers, supporting more refined risk stratification. Although interobserver variability remains a limitation, advances in AI-assisted pathology and preliminary studies on serum Ki-67 offer promising avenues for standardization and non-invasive assessment. Overall, Ki-67 plays an increasingly important role in grading, prognostication, and clinical decision-making in MTC, and may further enhance individualized disease management.