Malignant glioneuronal tumors of the brain are rare and poorly characterized. Herein, we report the clinicopathologic features of three examples with unusual morphologies including both glial and neuronal differentiation. Hematoxylin and eosin-stained slides were reviewed in all cases. Immunohistochemical stains were performed on formalin-fixed, paraffin-embedded sections. Transmission electron microscopy (EM) was performed on both formalin-fixed (n = 1) and paraffin embedded tissue (n = 2). The immunogold technique for localization of GFAP was also performed. Two patients were male and one was female, age 66, 84, and 34 years, respectively. Radiologic studies demonstrated hyperdensity on CT (n = 3), multicentricity (n = 2), and a cortical based solid component with a cystic extension into underlying white matter (n = 2). At surgery, all three tumors were superficial and relatively circumscribed. Histologically, they were composed of large epithelioid cells (n = 3), spindle cells (n = 1), and poorly differentiated smaller cells with high nuclear/cytoplasmic ratios (n = 1). Brisk mitotic activity and coagulative non-palisading necrosis were present in all cases. The tumors were immunopositive for GFAP (n = 3), S-100 (n = 3), synaptophysin (n = 3), chromogranin (n = 3), Neu-N (n = 2), and neurofilament protein (n = 2). Stains for EMA were negative. EM demonstrated convincing neurosecretory granules in one case, some in filament-containing cells immunogold labeled for GFAP. Two patients expired 3–5 weeks after surgery. True malignant neoplasms with glial and neuronal differentiation do occur in the central nervous system of adults and may pursue a highly aggressive course. The use of minimal diagnostic criteria, e.g., immunoreactivity for a single antigen like neurofilament protein, may not be sufficient and should be discouraged.