The early detection of colorectal cancer with effective screening is essential for reduction of cancer-specific mortality. The addition of fecal DNA testing in the armamentarium of screening methods already in clinical use launches a new era in the noninvasive part of colorectal cancer screening and emanates from a large number of previous and ongoing clinical investigations and technological advancements. In this review, we discuss the molecular rational and most important genetic alterations hallmarking the early colorectal carcinogenesis process. Also, representative DNA targets-markers and key aspects of their testing at the clinical level in comparison or/and association with other screening methods are described. Finally, a critical view of the strengths and limitations of fecal DNA tests is provided, along with anticipated barriers and suggestions for further exploitation of their use. The early detection of colorectal cancer with effective screening is essential for reduction of cancer-specific mortality. The addition of fecal DNA testing in the armamentarium of screening methods has in clinical use launches a new era in the noninvasive part of colorectal cancer screening and emanates from a large number of previous and ongoing clinical investigations and technological advances.. In this review, we discuss the molecular rational and most important genetic alterations hallmarking the early colorectal carcinogenesis process. Also, representative DNA targets-markers and key aspects of their testing at the clinical Finally, a critical view of the strengths and limitations of fecal DNA tests is provided, along with intended barriers and suggestions for further exploitation of their use.