The GA733 gene family is composed of GA733-1 (TROP2) and GA733-2 (Ep-CAM), whose expression has been examined in various carcinomas and reported to be significantly associated with prognosis. The aim of this study was to investigate the expression of GA733 gene family members and to compare their prognostic significance in pulmonary adenocarcinoma. One hundred thirty paraffin-embedded specimens of small-sized pulmonary adenocarcinoma, less than 2 cm in diameter, were categorized using the classification of small-sized pulmonary adenocarcinoma devised by Noguchi et al. (Cancer 75:2844-2852, 1995) and examined immunohistochemically using a murine monoclonal antibody against Ep-CAM and a goat polyclonal antibody against TROP2. The patient survival rate was calculated using the Kaplan-Meier method. Ep-CAM and TROP2 were similarly expressed in many small-sized pulmonary adenocarcinomas. The expression of Ep-CAM was significantly related to a favorable outcome (p = 0.0185), whereas TROP2 tended to be expressed in cases with an unfavorable outcome (p = 0.0564), and was significantly associated with an unfavorable outcome in nonlepidic-type adenocarcinomas (p = 0.0125). Multivariate analysis showed that TROP2 overexpression and lymph node metastasis were independent prognostic markers. Although the two GA733 proteins share structural similarity, they appear to have opposite biological significances in small-sized adenocarcinomas. As the expression of TROP2 was detected in more poorly differentiated tumors, the protein may have oncogenic activity.