Epithelioid and rhabdoid glioblastomas are rare entities that share some overlapping morphologic features, but remain poorly characterized at the immunohistochemical and genetic level. We report 10 examples: 8 epithelioid glioblastomas (E-GBMs) and 2 rhabdoid GBMs (R-GBMs). E-GBMs tended to be superficially located, circumscribed, supratentorial tumors composed of monotonous, discohesive sheets of small rounded cells that mimicked metastatic malignant melanoma. R-GBMs showed tumor with classic rhabdoid features arising as a subpopulation of an otherwise classic GBM, fitting the definition of composite extrarenal rhabdoid tumors. Polyphenotypic immunohistochemical expression and focal loss of INI-1 protein in the rhabdoid areas of R-GBMs distinguished them from E-GBMs. Monosomy 22 was identified in R-GBMs, but not E-GBMs. Immunostaining for claudin-6, a key component of tight junctions that we have earlier shown to be a positive cytoplasmic immunohistochemical marker for atypical teratoid or rhabdoid tumors (AT/RTs), was also conducted. None of the E-GBMs or R-GBMs showed claudin-6 cytoplasmic expression, including the focal areas in the 2 R-GBMs in which there was loss of INI-1 protein nuclear expression. Thus, in the CNS, claudin-6 expression may be a good discriminator of atypical teratoid or rhabdoid tumors from other CNS rhabdoid or epithelioid neoplasms.