An immunohistochemical study was made of the expression of c-myc protein, p53, c-erbB-2 protein and epidermal growth factor receptor (EGF-R) in human normal thyroid and thyroid tumors including follicular adenoma and follicular, papillary, squamous cell, anaplastic and medullary carcinoma. Immunoreaction product for c-myc protein was located in the cytoplasm as well as nucleus of follicular cells in normal thyroid and neoplastic cells of all tumors. Semiquantitative analysis using serial dilutions of the antibody showed significant differences in immunoreactive cytoplasmic c-myc protein between normal thyroid and thyroid tumors. Immunoreaction product for p 53 was noted in the cytoplasm of follicular cells in normal thyroid and neoplastic cells of all tumors, however, reaction product was absent in the nucleus for all cases of papillary and anaplastic carcinoma and 8 out of 10 cases of squamous cell carcinoma. On the other hand, normal thyroid and other types of thyroid tumor exhibited positive nuclear reaction for the antibody in about 50% of the cases. Immunoreaction product for c-erbB-2 protein and EGF-R was seen as either diffuse or granular deposits in the cytoplasm of the follicular cells in normal thyroid and neoplastic cells in all tumors, except for negative results in the immunostaining for EGF-R in normal thyroid. In immunostaining for these two antigens, thyroid tumor showed a significantly higher positivity than normal thyroid, and thyroid carcinoma showed a significantly higher incidence of positive cases than that of follicular adenoma, especially in immunostaining for EGF-R. These results show that cytoplamic c-myc protein, c-erbB-2 protein and EGF-R are enhanced in many cases of thyroid tumor, and EGF-R tends to increase considerably in thyroid carcinoma. It is also suggested that nuclear p53 might bear some relation to the differentiation of thyroid tumors.