Cancer stem cells (CSCs) play an important role in cancer development. Based on advancements in CSC research, we propose a monophyletic model of cancer. This model is based on the idea that CSCs are stem cells with disordered differentiation whose original purpose was to repair damaged tissues. Inflammatory responses and damage repair signals are crucial for the creation and maintenance of CSCs. Normal quiescent stem cells are activated by environmental stimulation, such as an inflammatory response, and undergo cell division and differentiation. In the initial stage of cancer development, stem cell differentiation leads to heteromorphism due to the accumulation of gene mutations, resulting in the development of metaplasia or precancerosis. In the second stage, accumulated mutations induce poor differentiation and lead to cancer development. The monophyletic model illustrates the evolution, biological behavior, and hallmarks of CSCs, proposes a concise understanding of the origin of cancer, and may encourage a novel therapeutic approach.Graphical Abstract