Background: Mass screening for colorectal cancer reduces mortality and, with recent advances in molecular genetics, molecular stool-based tests have produced promising results. This article reviews this innovation and discusses its clinical significance. Methods: Medline searches were used to identify recent key articles relating to stool-based testing. Further articles were obtained by manual scanning of the reference lists of identified papers. Results: Current screening methods are based on endoscopic, radiological and stool-based testing. Recent recognition of the adenoma-carcinoma sequence and pathophysiological studies of colonic epithelium have enabled tumour markers to be used in the screening setting. Non-invasive molecular stool testing has now been shown to have a high sensitivity and specificity. Conclusion: Recent studies on molecular stool-based testing have shown higher sensitivity and specificity than earlier studies, but larger clinical trials are required. Laboratory methods are still undergoing research, with the aim of improving sensitivity to allow large-scale testing.