Napsin A is a sensitive and specific marker for pulmonary adenocarcinoma versus squamous cell carcinoma. However, studies have shown that napsin A is also positive in approximately 5% of papillary thyroid carcinomas. The prevalence of napsin A in more aggressive types of thyroid carcinoma is unknown. Napsin A positivity in metastatic thyroid carcinoma, especially in conjunction with thyroid transcription factor-1 (TTF-1), could be misdiagnosed as lung adenocarcinoma. We investigated napsin A, TTF-1, and PAX8 expression in 26 anaplastic, 16 poorly differentiated, and 2 micropapillary pattern thyroid carcinomas. A focal micropapillary component was also present in 3 poorly differentiated and 3 anaplastic thyroid carcinomas. Four of 26 (15%) anaplastic, 2/16 (13%) poorly differentiated, and 2/2 (100%) micropapillary pattern thyroid carcinomas were napsin A positive. Three of the 6 cases (50%) with a focal micropapillary component were napsin A positive (1 of these 3 cases was positive only in the micropapillary component). All napsin A-positive cases were also positive for TTF-1, and all but 1 micropapillary pattern carcinoma were also PAX8 positive. In 1 case, napsin A was positive in the micropapillary component, but PAX8 was only positive in the adjacent poorly differentiated carcinoma. In summary, a minority of anaplastic and poorly differentiated thyroid carcinomas are napsin A positive. More importantly, napsin A expression is more common in carcinomas with a micropapillary component, a pattern shared in common with some lung adenocarcinomas. PAX8 may be diagnostically useful to distinguish these napsin A-positive thyroid carcinomas from lung adenocarcinomas, which are PAX8 negative.