Anaplastic astrocytoma is a high grade malignant glioma (WHO grade III) of the central nervous system which arises from a low grade II tumor and invariably progresses into lethal glioblastoma (WHO grade IV). We have studied differentially expressed proteins from the microsomal fraction of the clinical specimens of these tumors, using iTRAQ and high-resolution mass spectrometry followed by immunohistochemistry for representative proteins on tissue sections. A total of 2642 proteins were identified, 266 of them with minimum 2 peptide signatures and 2-fold change in expression. The major groups of proteins revealed to be differentially expressed were associated with key cellular processes such as post transcriptional processing, protein translation, and acute phase response signaling. A distinct inclusion among these important proteins is 10 heterogeneous nuclear ribonucleoproteins (hnRNPs) and their interacting partners which have regulatory functions in the cell. hnRNP-mediated post transcriptional events are known to play a major role in mRNA processing, stability, and distribution. Their altered levels have also been observed by us in lower (diffused astrocytoma) and higher (glioblastoma) grades of gliomas, and membrane localization of hnRNPs has also been documented in the literature. hnRNPs may thus be major factors underlying global gene expression changes observed in glial tumors while their differential presence in the microsomal fraction suggests yet additional and unknown roles in tumorigenesis.