The subjectivity in pathological diagnosis of anaplastic oligoastrocytoma (AOA) and uncertainty in designation of glioblastoma with oligodendroglioma component (GBMO) were two major dilemmas which puzzled neuro-pathologists and neurosurgeons. The present study was designed to project a molecular classification scheme based on the status of chromosome 1p and 19q. Patients (n = 117) with histological diagnosis of primary high-grade oligodendroglial tumors (HGOs) enrolled in the study. Fluorescence in situ hybridization (FISH) for chromosomes 1p and 19q was performed. Univariate analysis showed that higher tumor grade, 1p/19q maintenance and 1q/19p co polysomy were confirmed as risk factors in HGOs (P < 0.01). Accordingly, patients with HGOs were divided into four subtypes which conferred remarkably distinct prognosis based on the number of risk factors (0 risk factor: HGOs-1, 1 risk factor: HGOs-2, 2 risk factors: HGOs-3, 3 risk factors: HGOs-4). Cox regression model revealed that the tumor grade was no longer independently associated with survival, while the molecular classification scheme showed a marked prognostic significance (HR = 0.359, 95 % CI 0.261-0.494, P < 0.001 for progression-free survival (PFS); HR = 0.393, 95 % CI 0.283-0.546, P < 0.001 for overall survival (OS)). The classification scheme incorporating traditional pathology with molecular information can be served as a supplement of the current WHO classification system and contribute to the personalized treatment decision-making.