Organism is characterized by a remarkable plasticity, which drives efficient regeneration and restoration of homeostasis after damage. When aberrantly activated, this plasticity contributes to tumor initiation and progression. Both regenerative and tumorigenic processes rely on the coordinated integration at the tissue level of multiple forms of cellular plasticity. Understanding the mechanisms underlying the various forms of cell plasticity may deliver novel strategies for developing regenerative therapies, cancer prevention, and antitumor treatments.