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The accumulation of somatic mutations is the major driving force for tumorigenesis. These mutations uniquely differentiate tumor cells from their normal counterparts. Mutations within tumor cells and mutant DNA released by tumor cells into blood, lymph, stool, tissues and other bodily compartments can thereby be used for cancer detection. Here we discuss technologies available for the detection and quantification of mutant DNA in clinical samples and the value of such measurements for patient management.Conventional mutation detection technologies are either qualitative or only roughly estimate the abundance of mutant DNA molecules. Recently-developed approaches, however, use single molecule counting to determine the genotype of each individual member of a DNA population, providing a more accurate and precise digital output.In this review, we discuss the clinical utility of mutant DNA quantification in cancer patients in the context of recent technical advances made in digital mutation detection.