Thyroid tumorigenesis proceeds through the progressive accumulation of alterations in genes involved in the regulation of cell proliferation and differentiation accompanying the acquisition of phenotypic, biological and clinical characteristics of increasing malignancy and dedifferentiation. The molecular alterations specific to thyrocyte carcinogenesis are examined. Ras mutations seem to represent an early occurrence in thyroid tumorigenesis being common to both benign and malignant follicular tumors; they would represent the early mutational events able to enhance the cell proliferation. Subsequent alterations in several genes will probably result in the determination of a follicular or papillary phenotype. In particular, mutational events activating ret, met and trk thyrokinase receptors direct the tumor growth and development towards the papillary type. Progression towards a follicular phenotype would instead occur in two stages: first there is the loss of function of genes on chromosome 11q13 which may direct the tumor cell towards the phenotype of follicular adenoma, second, there is the inactivation of the probable suppressor oncogene on chromosome 3p which might be fundamental in the transition from adenoma to follicular carcinoma. Undifferentiated or anaplastic tumors are characterized by the presence of p53 gene mutations.