Differentiated thyroid cancer (DTC) is the most prevalent endocrine malignancy in the world. Accurate diagnosis and prognostication are essential for optimizing its treatment and improving patient outcomes. This narrative review explores the diagnostic and prognostic histopathological, immunohistochemical, molecular, and genetic biomarkers in DTC, emphasizing their role in risk stratification and personalized management. Histopathological biomarkers, including tumor size, extrathyroidal extension, lymphovascular invasion, and aggressive subtypes (e.g., tall cell, hobnail, and insular variants), correlate with poor prognosis. Additionally, genetic alterations such as :p.V600E, mutations, promoter mutations, and / rearrangements provide molecular insights into tumor progression and therapeutic response. Some of these molecular/genetic mutations have surrogate proteins that are feasible for immunohistochemical analysis, providing faster and cost-effective alternatives. Advances in next-generation sequencing have further refined risk stratification, facilitating precision medicine approaches. Future research should focus on validating novel biomarkers and developing targeted therapies to improve patient outcomes.