To clarify its biological nature, 10 samples of goblet cell-type adenocarcinoma of the lung were collected and compared with 10 other pulmonary mucin-producing adenocarcinomas with respect to immunohistochemical features and the presence of Ki-ras gene mutation in codons 12 and 13. Goblet cell-type adenocarcinomas lacked immunoreactivity for surfactant apoprotein and S-100 protein-positive Langerhans cells, which was in marked contrast to other mucin-producing adenocarcinomas. In addition, the mucin gene products, MUC-1 and MUC-2 glycoproteins were immunohistochemically stained. The results showed that MUC-1 glycoprotein is frequently expressed by mucin-producing adenocarcinomas except the goblet cell-type. Ki-ras gene mutation was detected in 12 of 20 (60%) mucin-producing adenocarcinomas. These mutations were exclusively found in codon 12 and G to A transitions were the most frequent type of alteration in the Ki-ras gene. In goblet cell-type adenocarcinomas, the frequency of Ki-ras gene mutation was 80% consisting of G to A transitions and G to T transversions in six and two tumors, respectively. Therefore, goblet cell-type adenocarcinomas differed from other mucin-producing adenocarcinomas in terms of immunohistochemical and molecular biological features, suggesting that goblet cell-type adenocarcinomas are distinctly different from other subtypes of adenocarcinomas.