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Purpose of ReviewColorectal cancer is increasingly recognised as a heterogeneous disease entity, and subtyping is carried out based upon clinical and pathological characteristics, individual somatic gene mutations and, more recently, gene expression profiling. This paper will discuss advances in the molecular stratification of colorectal cancer and the potential challenges and applications for real-world clinical management.Recent FindingsBeyond the established biomarkers of RAS and BRAF mutational status, a number of rarer genetic mutations have been identified, and trials are ongoing to identify and target these effectively. Differing subtyping systems based on gene expression profiling have also been proposed which have now been integrated into four consensus molecular subtypes, and the prognostic and predictive significance of these subtypes is being investigated. Molecular subtyping is methodologically challenging, and simpler classifier systems based on immunohistochemical correlate markers have been developed which may allow for wider clinical application.SummaryEmerging genetic biomarkers and gene expression-based molecular subtyping have increased understanding of the underlying biological complexity of colorectal cancer but have not significantly impacted upon clinical decision-making or treatment as yet. Prospective validation is required to establish their role in predicting response to existing and emerging therapies.