Small cell glioblastoma is a histological subtype of glioblastoma with characteristic features of highly proliferative, monotonous small glial cells with high nuclear cytoplasm ratio. Morphologically, malignant lymphoma or small cell metastatic carcinoma should be carefully discriminated. Some cases are difficult to differentiate from anaplastic oligodendroglioma. In this report, we present a case of small cell glioblastoma of an elderly man. The lack of IDH1/2 mutation was confirmed by immunohistochemistry and direct sequencing. Fluorescence in situ hybridization revealed the lower rates of chromosome 1p and 19q deletion. Microsatellite analysis disclosed partial 10q alteration near the PTEN locus. Not only morphological and immunohistochemical examinations, but also cytogenetical investigations for IDH1/2 mutation, 1p/19q loss, and PTEN alteration, are strongly supportive methods for the differential diagnosis of small cell glioblastoma and anaplastic oligodendroglioma.