Abstract: While surgical extirpation of colorectal cancer remains the primary modality for cure, patients who have metastasized to distant sites at the time of surgical intervention frequently die from their disease. Unfortunately, there is no accurate means of identifying the patients who are at risk for metastasis. Current staging systems, based only on clinicopathologic factors, are not very precise. Moreover, attempts at improving these staging systems, using molecular techniques to assay the expression of single or a small number of genes, have been relatively unsuccessful. This is likely because the process of metastasis is complex and linked to the expression of numerous gene families and pathways. Recently, methods have been developed which allow the analysis of gene expression for thousands of genes in a single experiment. We hypothesize that, by conducting comprehensive analyses of both RNA (microarray analysis) and protein (proteomic analysis) on the same tumor specimens, molecular fingerprints can be identified in primary tumors that portend metastasis. A three-party consortium between H. Lee Moffitt Cancer Center, The Institute for Genomic Research, and Large Scale Biology Corp. has been constructed to address this hypothesis. Based on the ubiquitous presence of endogenous ribonucleases, we predict that the success of this study will be based on our capacity to obtain fresh tissue specimens without significant ischemic effect. Tumors will be rationally selected to address the biological questions we have posed. And finally, statistical analyses designed for microarray analysis, which apply probability statistics to each and every expressed gene, will permit us to decipher specific fingerprints from complex datasets.