The origin and progression of cancer involves a sequence of genetic changes. However, evidence has been obtained with various types of tumors that malignant cells have not lost the genes that control normal growth and differentiation. Experiments are presented here on the induction of normal cell differentiation and restoration of the normal phenotype in myeloid leukemia by the physiological inducer of differentiation, i.e., the appropriate form of the macrophage and granulocyte that induces protein. The results of these studies can be therapeutically valuable. They have also been proposed as a general model for cell differentiation and the origin and progression of cancer.