Thyroid cancer surgery has evolved dramatically with advances in our understanding of the biological behaviour of WDTC. Molecular profiling is shedding light on the subset that may behave aggressively. In an era when thyroid cancer management is becoming increasingly conservative, decision making regarding the extent of surgery must be objectively guided by molecular markers. The aim of the present article is to summarise the current published literature and provide possible practice recommendations. An online search for relevant published articles was performed using several databases. Title, abstract, and full-text screening, along with data extraction, was performed by two independent reviewers after the inclusion and exclusion criteria were defined. A total of 1241 articles were identified, and 82 relevant articles were extracted and scrutinised. BRAF V600E and TERT promoter mutations were found to be associated with an increased risk of disease recurrence and distant metastases. Several other mutations have been identified that enhance disease aggressiveness (such as RET/PTC, PTEN, and TP53). One of the most important determinants of the outcome in WDTC is the extent of surgical resection. The evolution of molecular testing has reached a stage of personalised incorporation into surgical practice. Guidelines for molecular testing and surgery in WDTC will need to be clearly defined, arguably representing the next chapter in the management of the disease.