A key priority in translational cancer research is the discovery of molecular biomarkers that improve the early diagnosis of cancer and guide cancer prognosis, including the design and assessment of new therapeutic avenues. A Nature Insight in the current issue (Nature 452, 547-589; 3 April 2008) highlights key approaches for the discovery and validation of cancer biomarkers, at the level of DNA, RNA and protein analysis. It also focuses on non-invasive imaging tools and serum analyses that will be important in detecting tumours and monitoring the course of cancer therapy. Translating these advances into personalized cancer care will entail challenges far beyond the scientific discovery and validation strategies. We hope that the articles in this Insight not only bring together key aspects of the translational research into cancer biomarkers but also draw attention to associated issues such as trial design, tissue collection and regulatory requirements. This Nature Insight is freely available online for six months.