Craniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue. This epithelial tumor entity can be divided into the adamantinomatuous (ACP) and papillary (PCP) subtypes with the histomorphological and genetic differences. Genomic and transcriptomic profiles of craniopharyngiomas have been investigated, however the proteomic contribution to these profiles has yet to be elucidated. Recent improvement in high-throughput quantitative proteomic approaches have introduced new opportunities for a better understanding of these disease and an efficient discovering of biomarkers. In this study, we report a systems-level proteomic study of sub-type associated proteome changes in six specimens of ACP and five specimens of PCP using an integrated approach that combines mass spectrometry-based quantitative proteomics, statistical analysis, and bioinformatics analysis.