OBJECTIVE: To review the new research and further provide the relationship between monoclonal cell proliferation and tumor initiation and progression. STUDY DESIGN: Through analyzing the previous studies, we concluded the key factors of tumor cell initiation and proposed the dedifferentiation theory. RESULTS: Under normal cell communication, if the cell number in the monoclonal cell population exceeds one order of magnitude and there are no corresponding parent cells in this cell population, some cells in this population will dedifferentiate into parental cells and proliferate to keep a suitable proportion. The parental cells after dedifferentiation may have abnormal differentiation and lead to the abnormity of daughter cells. If the proliferative speed of abnormal daughter cells is faster than parental cells, the new monoclonal cell population will form and abnormal parental cells will form again, which promote the evolution of cell population. The malignant cells with stem cell characters are the initial cells of malignant tumors. For low-level benign tumors, the initial cells are those that do not survive for a long time and do not self-renew. CONCLUSION: The theory well explains the initiation and progression of cancer cells and cancer stem cells. © Science Printers and Publishers, Inc.