Epigenetic regulation is understood as heritable changes in gene expression and genome function that can occur without affecting the DNA sequence. In its in vivo context DNA is coupled to a group of small basic proteins that together with the DNA form the chromatin. The organization and regulation of the chromatin alliance with multiple nuclear functions are inconceivable without genetic information. With the advance on the understanding of the chromatin organization of the eukaryotic genome, it has been clear that not only genetics but also epigenetics influence both normal human biology and diseases. As a consequence, the basic concepts and mechanisms of cancer need to be readdressed and viewed not only locally but also at the whole genome scale or even, in the three-dimensional context of the cell nucleus space. Such a vision has a larger impact than has been previously predicted, since phenomena like aging, senescence, the entail of nutrition, stem cell biology, and cancer are orchestrated by epigenetic and genetic processes. Here I describe the relevance and central role of genetic and epigenetic defects in cancer.