High levels of RNases present in the normal pancreas and the abundance of desmoplastic stroma of most pancreatic cancers have traditionally caused difficulty in the extraction of high-quality RNA and gene expression profiling from pancreatic tissues. However, a variety of innovative strategies have made it possible to successfully perform a molecular analysis of pancreatic cancer, and the expression profiles that have been generated have provided tremendous insight into the nature of this aggressive disease. Here, we describe some of these techniques.