Background: Thyroid cancer is the most common endocrine cancer today. Differentiated thyroid cancer (DTC) comprises more than 95% of all thyroid cancers. With the increasing incidence of tumors and development of screening, more patients suffer from multiple cancers. The purpose of this study was to explore the prognostic value of a history of prior malignancy for stage I DTC.Methods: Stage I DTC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and Cox proportional hazards regression method were used to determine the risk factors for overall survival (OS) and disease-specific survival (DSS). A competing risk model was also used to determine the risk factors for DTC-related death after considering the competitive risks. In addition, conditional survival analysis in patients with stage I DTC was performed.Results: A total of 49,723 patients with stage I DTC were enrolled in the study, and 4,982 (10.0%) had prior malignancy history. Prior malignancy history was a factor affecting OS (P<0.001) and DSS (P<0.001) in the Kaplan-Meier analysis and an independent risk factor for OS [hazard ratio (HR) =3.6, 95% confidence interval (CI): 3.17-4.088, P<0.001] and DSS (HR =4.521, 95% CI: 2.224-9.192, P<0.001) in the multivariate Cox proportional hazards regression analysis. In the competing risk model, in the multivariate analysis, prior malignancy history was a risk factor for the DTC-related deaths [subdistribution HR (SHR) =4.32, 95% CI: 2.233-8.3593, P<0.001] after considering the competitive risks. Conditional survival showed that the probability of achieving 5-year DSS was not changed in either the two groups with or without prior malignancy history. For the patients with prior malignancy history, the probability of achieving 5-year OS increased with each additional year survived, but for the patients without prior malignancy history, the improvement of conditional OS only appeared with 2 years already prior survived.Conclusions: Prior malignancy history has an adverse impact on the survival of patients with stage I DTC. The probability of achieving 5-year OS for stage I DTC patients with prior malignancy history increases with each additional year survived. The inconsistent survival effects of prior malignancy history should be considered in clinical trial and recruitment.