Purpose: Brain metastasis (BM) in patients with differentiated thyroid cancer (DTC) are rare but associated with poor prognosis. We examined risk factors for overall survival (OS) in this population and explored the pattern of genomic alterations. Materials and Methods: Single institution, retrospective review of all patients with DTC from January 2000-November 2016, identified 79 patients for analysis. Multiple prognostic factors, including age, gender, distal metastasis (DM), diagnosis time, DM sites, BM diagnosis time, BM number and size, genomic sequencing data, craniectomy, external beam radiation (EBRT), and kinase inhibitor therapies were evaluated. Univariate and multivariate analyses were performed. Results: Median survival after BM was 18 months. One-and three-year survival was 63% and 33% respectively. Univariate analysis identified four covariates correlated with prolonged survival: time between DTC diagnosis and BM < 3 years (p = 0.01), time from initial DM diagnosis to BM ≤ 22 months (p = 0.03), ≤ 3 BM sites (p = 0.002), and craniectomy (p = 0.05). Multivariate model revealed three variables associated with OS: DTC diagnosis to BM time < 3 years (p = 0.04), *