The multistep nature of cancer has been well-documented through molecular genetic studies of colorectal cancer. The information provided by basic, translational and clinical science highlighted several genes associated with different hereditary syndromes predisposing to colorectal cancer. Due to these and other findings, the molecular pathogenesis of this cancer has been clarified also with respect to genetic pathways which can lead to an otherwise undistinguishable disease. As a result of both the available and continuously added data, our knowledge and understanding of colorectal cancer is subject to constant changes. Ultimately, these are expected to result in multiple and strategical managements based on molecular genetics which will likely change our approach to this cancer in the incoming millennium.