BACKGROUND: There has been renewed interest in extensive lymph node dissection for papillary thyroid cancer (PTC), and a number of reports have been published concerning compartment-oriented dissection of regional lymph nodes in PTC. A comprehensive review of this body of literature using evidence-based methodology is pending. METHODS: Systematic review of the literature using evidence-based criteria. RESULTS: Issue 1: Systematic compartment-oriented central lymph node dissection (CLND) may decrease recurrence of PTC (Levels IV and V data, no recommendation) and likely improves disease-specific survival (grade C recommendation). Limited level III data suggest survival benefit with the addition of prophylactic dissection to thyroidectomy (grade C recommendation). The addition of CLND to total thyroidectomy can significantly reduce levels of serum thyroglobulin and increase rates of athyroglobulinemia (level IV data, no recommendation). Issue 2: There may be a higher rate of permanent hypoparathyroidism and unintentional permanent nerve injury when CLND is performed with total thyroidectomy than for total thyroidectomy alone (grade C recommendation). Issue 3: Reoperation in the central neck compartment for recurrent PTC may increase the risk of hypoparathyroidism and unintentional nerve injury when compared with total thyroidectomy with or without CLND (grade C recommendation), supporting a more aggressive initial operation. CONCLUSION: Evidence-based recommendations support CLND for PTC in patients under the care of experienced endocrine surgeons.