Not all Glioblastoma multiforme (GBM, grade IV WHO) manifest the same clinical course. Different prognostic classes may arise from different morphologic and genetic profiles. The observation of oligodendroglial foci within GBM samples and their correlation with genetic alterations may predict a better prognosis. 450 patients affected by histologically proven supratentorial cerebral GBM were treated at our institutions from January 2000 to December 2006: all patients received at least subtotal surgical removal, followed by the same standard radio-chemotherapy adjuvant treatment. In a subgroup of 36 patients (8.0%) an oligodendroglial component was observed. Molecular assessment of these cases was performed and LOH for 1p, 19q and 10q, EGFR amplification and TP53 gene expression was determined. Median age of this subgroup was 52.1 years (range: 29-78 years) vs 62.4 years in the entire GBM population. Chromosome analysis resulted as follows: LOH 1p and/or 19q in 27 cases (75.0%), LOH of 10q in 21 cases (58.1%), EGFR amplification in 14 cases (39%) and TP53 mutation in eight patients (22.2%). OS was of 20.9 months while it was 13.6 months in the entire GBM population. Progression free survival (PFS) was 10.3 months and 7.6 months the entire group. Two-year survival was of 55%. The presence of an oligodendroglial component in GBM appears to be an important prognostic factor to which better prognosis can be related. LOH 1p and 19q was significantly associated with GBM with oligodendroglial component.