OBJECTIVE: The purpose of this study was to identify the risk factors that predict papillary thyroid microcarcinoma (PTMC)-related death in a large patient population to determine which patients need aggressive treatment. BACKGROUND: The management of PTMC is controversial and ranges from observation to total thyroidectomy. The lack of consensus is predominantly due to the general excellent overall prognosis, thereby requiring a large cohort to delineate differences in outcome. METHODS: All papillary thyroid cancer patients with tumor size of 1 cm or less in the Surveillance, Epidemiology and End Results Cancer Database from 1988 to 2007 were identified. Outcomes, including overall and disease-specific survival, were compared, and different risk groups were evaluated by multivariate analysis. RESULTS: A total of 18,445 cases of PTMC with surgery were identified. The 10-year and 15-year overall survivals were 94.6% and 90.7%, respectively, while disease-specific survivals were 99.5% and 99.3%. Age greater than 45 years, male sex, African American or minority race, node metastases, extrathyroidal invasion, and distant metastases were stratified to be significant risk factors for overall survival. There were 49 thyroid cancer-related deaths. Forty-five (92%) of the 49 patients had at least 2 risk factors, and 51% of these 49 patients had 3 or more risk factors (vs 5.7% in the rest of the cohort, P < 0.001). CONCLUSIONS: Although PTMC is generally associated with an excellent prognosis, 0.5% patients may die of PTMC. The presence of 2 or more risk factors is strongly associated with cancer-related mortality and can help to identify patients who should be considered for more aggressive management. Copyright © 2011 by Lippincott Williams & Wilkins.