To determine the methylation status of gene promoter regions using methylation-specific polymerase chain reaction in genes encoding for thyrotropin receptor (TSHR), E-cadherin (ECAD), sodium iodide symporter protein (NIS-L), ataxia telangiectasia mutated (ATM), and death-associated protein kinase (DAPK) proteins and if methylation status correlates with patient variables, tumor factors, or outcome measures among patients with papillary thyroid carcinoma. Design: Database query and retrospective medical chart review for patients with well-differentiated thyroid cancer and nonmalignant thyroid conditions treated at our institutions (1996-2004). Methylation-specific polymerase chain reaction was performed, and results were compared with controls for these genes. Methylation status was then compared with patient variables, tumor factors, and outcome measures for patients with thyroid carcinoma and controls. Patients: The study population comprised 32 patients with papillary thyroid carcinoma and 27 controls. Results: In our patients, all 5 genes were methylated more frequently in papillary thyroid carcinoma than in controls. NIS-L trended toward a more advanced stage at presentation. NIS-L methylation in cancer cells was not associated with methylation in adjacent benign tissue, unlike the other 4 genes. Neither age nor sex affected methylation status, and methylation status did not correlate with extent of the primary tumor or presence of nodal metastasis at diagnosis. Tumors recurred less frequently in patients with TSHR methylation than in patients with unmethylated TSHR promoter regions. Conclusions: Promoter methylation may be a marker for malignancy in thyroid carcinoma. Furthermore, methylation status of tumors as determined by methylationspecific polymerase chain reaction may help in determining patient prognosis.