The nuclear immunoreactivity for thyroid transcription factor-1 (TTF-1) is a useful marker for identification of carcinomas of thyroid and lung origin. Our aim was to determine whether cytoplasmic staining in the liver is a result of cross-reaction of anti-TTF-1 antibody (clone 8G7G3/1, DAKO, Carpinteria, CA) or true positivity resulting from aberrant expression of TTF-1 or products of the alternatively sliced TTF-1 gene. Fresh tissue samples from liver, thyroid, and lung were obtained for H&E-stained sections, TTF-1 immunostaining, and RNA and protein analyses. Western blot revealed an abundant band corresponding to an approximately 160-kd protein from liver but not either thyroid or lung tissue samples. By reverse transcriptase-polymerase chain reaction, messenger RNA of TTF-1 was not detectable in liver tissue. Our study demonstrates that TTF-1 immunoreactivity (clone 8G7G3/1) in the hepatocyte cytoplasm is due to an approximately 160-kd protein; this unique protein is not an alternative splicing product of TTF-1 and neither is it expressed in thyroid and lung tissues.