The present review summarizes our strategies aimed at identifying and characterizing genetic alterations occurring at the transcriptional and chromosomal level in pancreatic cancer. To study transcriptional alterations we have used a number of techniques including modified versions of differential hybridizations and cDNA RDA (representational difference analysis). These approaches have led to the identification of more than 500 genes with differential expression in pancreatic cancer. To study chromosomal aberrations occurring in pancreatic cancer tissues we used comparative genomic hybridization (CGH). This allowed the identification of a number of chromosomal regions containing putative tumor suppressor genes or oncogenes. Genes isolated in both approaches represent potential new disease genes for pancreatic cancer and are at present being characterized by individual or serial analysis.