Medulloblastoma (MB) is recognized as comprising four molecular subgroups with distinct transcriptional profiles, clinical features, and outcomes. Previous studies demonstrate that pediatric MBs present with subgroup-specific MRI manifestations. We hypothesized that combination of anatomical localization and conventional features based on MR imaging can predict these subgroups in adult MBs. MR Imaging manifestations of 125 adult patients with MB were analyzed retrospectively based on pre-operative MRI scans. MB molecular subgroups were evaluated by the expression profiling array and immunohistochemistry. A pediatric MB cohort of 60 patients were analyzed for comparison with data of adult patients. Multiple logistic regression analysis revealed that tumor location (P < 0.0001) and pattern of enhancement (P = 0.0048) were significantly correlated with molecular subgroups in adult MBs. Ninety-two percent of adult MBs were correctly predicted by using logistic regression model based on the anatomical localization patterns and pattern of enhancement. Exclusively intra-cerebellar growth, localization in the rostral cerebellum, and no brainstem contact were specific to adult SHH-MBs. Group 4-MBs in adult were characterized by minimal/no enhancement compared with other two subgroups. Infant SHH-MBs represented significant different localization patterns compared with SHH tumors in children and adults. We identified that molecular subgroups of adult MBs could be well predicted by tumor localization patterns and enhancement pattern. Our study also provided important evidence that MB subgroups in adult possibly derived from different cellular origins.