The identification of molecular markers with prognostic value in colorectal cancer is a challenging task that is needed to define therapeutic guidelines. Clinical factors are insufficient to identify those patients with stage II at risk of relapse or those patients with stage III at low risk. There is a current effort to define a consensus in molecular subtypes based on expression profiles, which are characterized by a distinctive prognostic outcome. Also several gene expression signatures based on individual genes have been proposed to predict prognosis, but they show low consistency and reproducibility. Slattery et al. describe a pathway-based approach to analyze gene expression differences between normal and colon cancer tissues. The most interesting finding is that having more deregulated pathways is associated with good prognosis. If these findings are properly validated, new insights into the mechanisms of colon carcinogenesis may be revealed.