Thyroid anaplastic (undifferentiated) carcinomas (TACs) comprise a morphologically heterogeneous group of tumors, which can arise in the background of differentiated papillary or follicular carcinoma. The thyroid epithelial differentiation varies in these tumors and has not been completely characterized. In this study, we immunohistochemically analyzed different variants TACs from 35 patients by using antibodies specific to 9 different keratin polypeptides, epithelial membrane antigen, thyroid transcription factor I (TTF-1), and thyroglobulin. These tumors were histologically divided into 3 categories: squamoid-cohesive (SC, 13 tumors), spindle cell sarcomatous (SS, 8 cases) and intermediate group, including tumors with giant cells and solid epithelioid components (GC, 18 tumors); 4 tumors had 2 components. The patients ages ranged from 40 to 89 years, with a mean age in all groups of 70 years. TTF-1 was present in only 2 of 9 of the SC tumors, and absent in all other TACs, but was present in entrapped differentiated components. Thyroglobulin was absent in all but 1 case. A complex keratin (K) pattern of stratified epithelia was typically seen in the SC tumors with extensive K7, K8, K17, K18, and K19, and variable K13 and K14 expression; EMA was also present. K16 was limited to squamous pearls in 1 tumor, and K10 was absent. The GC carcinomas typically had K8 and K18, whereas the expression of K7 was variable and that of K14, K17, and K19 sporadic; EMA was variably present in half of the cases. The keratins in spindle cell sarcomatous tumors were usually limited to K7, K8, and K18, often in limited numbers of cells. EMA was present in 1 case only. These results indicate a complex pattern of keratins in squamoid and giant cell TACs, similar to papillary carcinoma and suggesting the possibility of relationship. There was a progressive loss of epithelial differentiation and keratins in sarcomatoid TACs. Loss of TTF-1 is a nearly uniform feature of TAC and disallows the use of this marker to pinpoint a thyroid origin of these tumors.