The existence of angiosarcoma (AS) of the thyroid has been a matter of debate for many years, because some authors believe that most if not all ASs are in fact "angiomatoid" anaplastic carcinomas (ACs). Immunohistochemistry alone was not successful in solving the problem, since cytokeratin expression is a known occurrence in AS. Therefore, we wanted to compare nine cases of AS with ten cases of AC, assessing whether thyroglobulin (TG) mRNA was still transcribed in undifferentiated tumors and could be helpful to distinguish AC from AS. The cases were analyzed for TG mRNA expression by means of radioactive in situ hybridization. The silver grains were counted using an automated device, and their amount was compared with that of stroma, background, and peritumoral thyroid. A weak signal was present in all AC but not in AS (mean counts 35.7 and 9.6 arbitrary units, respectively: P<0.01). In two cases of AC, residual areas of poorly differentiated insular carcinoma had a strong signal (similar to that of peritumoral thyroid). These findings further confirm that AC and AS of the thyroid are unrelated malignant tumors.