Genomic damage present in tumors may lead to abnormal or altered expression of proteins. Some of the findings of genetic explorations of brain tumors have had their impact on making the diagnosis or are important with respect to therapeutic decisions. The identification of individual proteins or clusters of proteins expressed in neoplastic tissues potentially may have an even more important relevance for making the diagnosis, prognosis and treatment outcome. Diverse posttranslational modifications of proteins may be linked to neoplastic lineage or stage. For the rapidly developing fields of proteomics and its integration with genomics and transcriptomics (by now called operomics) the application of bioinformatics is crucial. This review addresses the nascent field of proteomics and its diagnostic potential in the feld of primary brain tumors. Various technical approaches to separate and identify proteins are described, including the most recent developments in the analytical proteomic technology.