BACKGROUND: Simultaneous medullary thyroid carcinoma (MTC) and differentiated thyroid carcinoma (DTC) is a rare entity. This is the first population-level analysis of the characteristics and outcomes of simultaneous MTC/DTC. METHODS: In the Surveillance, Epidemiology, and End Results (SEER) database (1988-2008), patients with simultaneous MTC/DTC were retrospectively compared with those with MTC alone using χ(2), ANOVA, log-rank tests, Cox multivariate regression, and Kaplan-Meier analyses. RESULTS: A total of 162 patients had simultaneous MTC/DTC; 1,699 had MTC alone. MTC was diagnosed first in 67.9 % of simultaneous MTC/DTC cases. Simultaneous MTC/DTC increased from 2.7 % of all MTCs in 1988-1997 to 12.3 % in 2003-2008. Compared with MTC alone, simultaneous MTC/DTC had smaller mean MTC tumor size (2.9 vs. 2.2 cm; p = 0.005) and lower rates of MTC extrathyroidal extension (25.4 vs. 16.8 %; p = 0.015) and distant metastases (15.7 vs. 9.3 %; p = 0.032). Patients diagnosed with DTC first had smaller mean MTC tumor sizes (p = 0.01), whereas patients diagnosed with MTC first had tumor sizes similar to those of MTC alone. Compared with MTC alone, patients with simultaneous MTC/DTC were more likely to receive thyroidectomy (84.7 vs. 93.2 %; p = 0.003) and radioisotopes (4.4 vs. 25 %; p < 0.001). On Kaplan-Meier analysis, disease-specific survival rates were higher for simultaneous MTC/DTC than for MTC alone (10-year survival rates 87 vs. 81 %; p = 0.056). CONCLUSIONS: Simultaneous MTC/DTC is diagnosed earlier in tumor development than MTC alone, with a trend toward better prognosis. This entity likely represents a primary tumor with an incidental pathologic finding of a second malignancy. Each malignancy should be treated according to its respective stage and current guidelines.