The Apc^Min/+ mouse is a popular animal model for studies of human colon cancer, but the molecular changes associated with neoplasia in this system have only been partially characterized. Our aim was to identify novel genes involved in tumorigenesis in this model. RNA from intestinal adenomas and from pre‐neoplastic small intestine were prepared from six Apc^Min/+ mice. The tumor transcriptomes were analyzed with high‐density oligonucleotide microarrays representing ∼12,000 probe sets; we compared their profiles with those of matched pre‐neoplastic intestine. Stringent analysis revealed reproducible changes for 98 probe sets representing 90 genes, including novel observations regarding 50 genes whose involvement in this mouse model has never been reported. In addition to the expected changes in growth regulatory genes, the altered gene products could be assigned to four functional groupings that should enhance tumorigenesis: metabolic changes that would result in a high rate of glycolysis, alterations in enzymes involved in reactive oxygen species or carcinogen metabolism, cytoskeletal elements, and proteins involved in tumor invasion or angiogenesis. A fifth group consisted of expression changes that might restrict tumor progression, suggesting that the adenomatous state reflects a balance of pro‐ and anti‐tumorigenic factors. Since many of the altered genes had not previously been reported to be involved in any tumorigenic processes, our observations provide a host of new candidates for potential modulation to prevent or treat intestinal neoplasia. Supplementary material for this article can be found at http://www.mrw.interscience.wiley.com/suppmat/0730‐2312/suppmat/v93.html. © 2004 Wiley‐Liss, Inc.