In order to address the molecular signature of human glioma, we investigated the polymorphism of 5'UTR of the mRNA of Contactin, an adhesion molecule which plays a role in the invasive behavior of these tumors. Contactin mRNA is identified by RT-PCR and a strategy based on rapid amplification of cDNA ends (RACE) reveals different 5'UTRs resulting from both an alternative use of two types of leader exons and a splicing mechanism within the 5'UTR. The spliced exon is an Alu-containing element specific to the primate lineage, thus indicating a recent evolution of regulatory processes specific to the simian line that occurs on this gene. Each 5'UTR exhibits different transcription/translation efficiencies and contains features that allow translation to occur independently of the classic cap-dependent mechanism. These data illustrate the complex regulation of Contactin expression in human brain tumors occurring at both transcriptional and translation levels. The different 5'UTRs are differentially expressed in diverse types of human tumors. Thus, the polymorphism occurring within the non-coding part of the Contactin mRNA reveals new opportunities to explore deregulation that occurs during the oncogenic process.