It has traditionally been accepted that, in the process of cellular differentiation, developmental options are progressively restricted until commitment to a specific fate is established and then only terminal differentiation along this lineage is possible. Although this is usually the case in normal physiological development, the latest experimental evidences indicate that the differentiated state of mature cells is not always as stable and durable as it was thought to be. In fact, recently, a hidden plasticity has been revealed in differentiated cells which allows them to deviate to other cell types that might be, functionally, very far away in other developmental pathways. This plasticity has biological significance since it is necessary for normal development to occur, but it also makes possible the emergence of aberrant lineages when interferences with the normal transcriptional and epigenetic mechanisms in charge of maintaining cellular identity do appear. Cancer is one of the possible outcomes of this aberrant reprogramming. The plasticity of the initial cell suffering the first oncogenic alteration plays an essential role in cancer development, since only if this cell possesses enough plasticity a tumoral reprogramming will be possible and a full-blown tumor will develop. Also, plasticity makes it possible for differentiated cells to acquire cancer stem cell properties in the presence of the appropriate oncogenic insults. In this review we discuss the role of cellular plasticity in the normal development of adult tissues and how cellular susceptibility to reprogramming plays an essential part in cancer development.