The elucidation of the genetic basis of cancer is the result of the research conducted since the beginning of the previous century, which peaked during the decades of 1960s and 1970s. It has been achieved through two different but convergent routes: the first includes the study of oncogenic viruses in rodents and birds and the second includes the use of chemical carcinogens in cells or in animal model systems (mice). Within this framework, the identification of genes that present mutations, alterations in expression levels, and epigenetic modifications has been facilitated through the development of animal carcinogenesis models. One of these models is the well-characterized mouse multistage skin cancer system discussed in this review. In addition, recent evidence shows the great significance that cancer stem cells seem to have in the emergence and progression of carcinogenesis. Finally, herein we discuss the critical role that miRNAs have emerged to play in cancer progression. miRNAs emerged as molecules with an impact on most cancer-related cellular processes, involving cell proliferation, cell death (apoptosis), angiogenesis, migration/motility, and rearrangement of the cytoskeleton. Their discovery has given rise to studies with a focus on miRNAs as key players in crucial oncogenesis-related processes and thus as potential targets in cancer therapeutics.