Objective: The purpose of this study was to evaluate variations in the regional incidence of glioblastoma in US adults in 2004–2013.Study Design and Setting: We evaluated 24,262 patients with primary glioblastoma. Data were categorized based on geographic regions that included different SEER registry sites as follows: (1) Northeast: Connecticut, New Jersey (3,977 patients); (2) South: Kentucky, Louisiana, Metropolitan Atlanta, Rural Georgia, Greater Georgia (excluding AT and RG) (5,212 patients); (3) North Central: Metropolitan Detroit, Iowa (2,320 patients); (4) West: Hawaii, New Mexico, Seattle (Puget Sound), Utah, San Francisco-Oakland SMSA, San Jose-Monterey, Los Angeles, Greater California (excluding SF, LA, and SJ), Alaska (12,753 patients).Results: Statistically significant differences in the rates of overall patient survival (P < 0.001) and the incidence of glioblastoma (24.31, 22.6, 20.35, 15.03 per 100,000/year in the South, Northeast, West, North Central regions, respectively) were identified between geographic regions. Multivariate Cox regression analysis demonstrated that overall survival was better in patients of Asian or Pacific Islander race. In addition, age, registry site, marital status, tumor laterality, histological classification, the extent of disease, tumor size, tumor extension, and treatment methods were identified as significant prognostic factors.Conclusion: Glioblastoma incidence is geographic region and race/ethnicity–dependent.