To evaluate whether genes identified by SINCE-PCR as differentially expressed during normal colon differentiation can be used as prognostic markers for colon cancer patients, we analyzed a pooled database of 299 primary colon cancer gene-expression arrays annotated with disease-free survival (DFS) data (Jorissen and Smith, ). First, we used the Hegemon software to graph individual arrays according to the expression levels of KRT20 and one of four genes characteristic of “top-of-the-crypt” CA1+/SLC26A3+ enterocyte-like cells (A, CA1; D, MS4A12; G, CD177; J, SLC26A3) and we exploited the StepMiner algorithm to define gene-expression thresholds. In all four instances, three distinct gene-expression groups could be visualized: Group 1 (green), defined as KRT20+/CA1high, KRT20+/MS4A12 high, KRT20+/CD177+ or KRT20+/SLC26A3+, respectively; Group 2 (blue), defined as KRT20+/CA1neg/low, KRT20+/MS4A12neg/low, KRT20+/CD177neg or KRT20+/SLC26A3neg, respectively; Group 3 (red), defined as KRT20neg/CA1neg/low, KRT20neg/MS4A12neg/low, KRT20neg/CD177neg or KRT20neg/SLC26A3neg, respectively. In all instances, an increasingly immature gene-expression profile corresponded to a progressively worse prognosis (B, F, H, K). Multivariate analysis of survival data indicated that the prognostic effect of these “gene-expression groups” is not confounded by clinical stage, age or sex (C, F, I, L; * p < 0.05, ** p < 0.001).