α-Internexin (INA) has been proposed to be a surrogate marker for the 1p/19q codeletion in oligodendroglial tumors (OTs). We analyzed INA expression in 83 glioma and 21 oligodendroglial phenotype-mimicking tumors (OMT) to assess its usefulness in differential diagnosis and its correlation with 1p/19q status; in particular, INA expression in gliomas with isolated/partial 1p or 19q deletions was assessed. α-Internexin expression and 1p/19q codeletion were present in 92% (34/37) of codeleted tumors (p < 0.0001). By contrast, INA was found in only 20% of cases with isolated/partial 1p aberrations and 36% of cases without 1p/19q deletions; it was also foundin 63% (10/16) of cases with isolated/partial 19q aberrations. α-Internexin expression was more specific in high-grade than in low-grade gliomas (66% vs 31%). Notably, a subset of tumors (10/83) displayed a biphasic INA expression pattern that was significantly associated with proliferation rate, whereas all areas harbored the 1p/19q codeletion. Only no or weak INA expression was seen in OMTs. In summary, INA is a useful marker to differentiate OTs from astrocytic tumors and OMTs, but INA expression is not exclusively linked to OTs harboring the 1p/19q codeletion. Moreover, it can sometimes be heterogeneously distributed within tumors, which emphasizes the need for 1p/19q analysis by molecular genetic techniques for diagnosis.