Despite the clonal origin of most tumors, their tremendous heterogeneity suggests that cancer progression springs from the combined forces of both genetic and epigenetic events, which produce variant clonal populations, together with the selective pressures of the microenvironment, which promote growth and, perhaps, dissemination of variants with a specific set of characteristics. Although the importance of genetic mutations in cancer has long been recognized, the role of epigenetic events has been suggested more recently. This review focuses on the genetic and epigenetic molecular mechanisms involved in cancer onset and progression, and discusses the possibility of new strategies in the development of anticancer treatments.