The review discusses the significance of the BRAF mutation in thyroid cancer. The T1799A BRAF mutation is the most common genetic alteration in thyroid cancer, particularly in papillary thyroid cancers (PTCs), and is mutually exclusive with other common genetic alterations. This mutation is associated with a poorer clinicopathological outcome and serves as a specific diagnostic marker for PTC. The mutation is also mutually exclusive with RET/PTC rearrangements and displays a reciprocal age association. The review highlights the potential of BRAF mutation detection in fine-needle aspiration biopsy (FNAB) specimens for diagnosing thyroid cancer, especially in cases with indeterminate cytology. Additionally, the mutation's prognostic value is discussed, suggesting it as an independent prognostic factor for poor outcomes in PTC. Finally, the therapeutic potential of inhibiting the MAP kinase pathway using novel inhibitors is explored, particularly for treating inoperable and radioiodine-resistant thyroid cancers, including ATC.The review discusses the significance of the BRAF mutation in thyroid cancer. The T1799A BRAF mutation is the most common genetic alteration in thyroid cancer, particularly in papillary thyroid cancers (PTCs), and is mutually exclusive with other common genetic alterations. This mutation is associated with a poorer clinicopathological outcome and serves as a specific diagnostic marker for PTC. The mutation is also mutually exclusive with RET/PTC rearrangements and displays a reciprocal age association. The review highlights the potential of BRAF mutation detection in fine-needle aspiration biopsy (FNAB) specimens for diagnosing thyroid cancer, especially in cases with indeterminate cytology. Additionally, the mutation's prognostic value is discussed, suggesting it as an independent prognostic factor for poor outcomes in PTC. Finally, the therapeutic potential of inhibiting the MAP kinase pathway using novel inhibitors is explored, particularly for treating inoperable and radioiodine-resistant thyroid cancers, including ATC.