We report a case of *-fetoprotein (AFP)-producing pulmonary carcinoma with studies for messenger RNA (mRNA) expression of hepatocyte nuclear factor (HNF)-4*, which is a transcription factor that is highly expressed in the process of liver development. The patient was a 64-year-old man with a pulmonary tumor in his left lower lobe. Serum AFP was 673 ng/mL. The microscopic analysis of the surgical specimen revealed a large cell neuroendocrine carcinoma with occasional hepatoid foci. The competitive reverse transcriptase polymerase chain reaction analysis revealed that HNF-4* mRNA was expressed on the order of 10(2)- to 10(3)-fold more abundantly than control pulmonary carcinomas and normal lung tissues. In addition, AFP and HNF-4* expression was restricted in hepatoid foci. Two previously reported cases of AFP-producing pulmonary carcinoma were also positive, whereas all 18 control pulmonary carcinomas were negative for HNF-4*. These findings suggest that aberrant expression of HNF-4* is implicated in the emergence or maintenance of hepatoid foci in AFP-producing pulmonary carcinomas.