Colorectal cancer is one of the most common cancers in the world. Histological staging is efficient, but combination with molecular markers may improve tumor classification. Gene expression profiles have been defined as prognosis predictors among stage II and III tumors, but their implementation in medical practice remains controversial. Stage II tumors have been recognized as a heterogeneous group, and high-risk morphologic features have been used to justify adjuvant chemotherapy. We propose here the investigation of clinical features and expression profiles from stage II and stage III colon carcinomas without DNA mismatch repair defects. Two series of 130 and 66 colon cancer samples were obtained. Expression profiles were established on oligonucleotide microarrays and processed in the R/Bioconductor environment. Hierarchical, then supervised, analyses were successively performed by applying a data-sampling approach. A molecular signature of seven genes was found to cluster stage III tumors with adjusted p values lower than 10(-10). A subgroup of stage II tumors aggregated this cluster in both series. No correlation was found with disease severity, but the function of the discriminating genes suggests that tumors have been classified according to their putative response to adjuvant targeted or classic therapies. Further pharmacogenetic studies might verify this observation.