To uncover mechanisms underlying progression of colorectal carcinogenesis and to identify genes associated with liver metastasis, we analyzed expression profiles of 14 primary colorectal cancers (CRCs) with liver metastases, and compared them with profiles of 11 non-metastatic carcinomas and those of 9 adenomas of the colon. A hierarchical cluster analysis using data from a cDNA microarray containing 23,040 genes indicated that the cancers with metastasis had different expression profiles from those without metastasis, although a number of genes were commonly up-regulated in primary cancers of both categories. We documented 54 genes that were frequently up-regulated and 375 that were frequently down-regulated in primary tumors with metastases to liver, but not in tumors without metastasis. Subsequent quantitative PCR experiments confirmed that PRDX4, CKS2, MAGED2, and an EST (GenBank accession number BF696304) were expressed at significantly higher levels in tumors with metastasis. These data should contribute to a better understanding of the progression of colorectal tumors, and facilitate prediction of their metastatic potential.