The appropriate initial extent of surgery for localized papillary thyroid cancer (PTC) remains controversial as current risk-stratification paradigms are largely based on final pathology. Further understanding of the molecular pathogenesis of thyroid cancer has led to an era of increased molecular testing of thyroid nodules to aid in both diagnosis and prognosis. Although the utility of molecular testing in the diagnosis of indeterminate thyroid nodules has been validated, the extent to which molecular data can determine prognosis and guide the initial extent of thyroidectomy remains unclear. Recent literature assigning patients with thyroid cancer to molecular risk groups (MRGs) based on mutational profile have favored hemithyroidectomy for PTCs within the lowest MRG and total thyroidectomy for PTCs within highest MRG in the absence of other clinically known risk factors. Most patients, however, exist within the indeterminate MRG, in which the impact of molecular testing upon the extent of surgery remains unknown and will require further investigation.