Cyclooxygenase (Cox)-2 plays an important role in cell proliferation, carcinogenesis and tumor growth, in part through the synthesis of prostaglandin E2 (PGE2) as well as through other yet unknown routes. Epidermal growth factor receptor (EGFR) signaling regulates Cox-2 expression, which has not been thoroughly examined in bronchial carcinomas. The current study examined the expression of Cox-2, EGFR, P53 and proliferative marker Ki-67 immunoreactivities by immunohistochemistry in 71 surgically removed stage I bronchial adenocarcinomas. Furthermore, we evaluated the prognostic value of these molecules to elucidate the biological significance of Cox-2 expression. Higher Cox-2 expression (more than 10% immunoreactivities in tumor cells) was strongly associated with higher EGFR and P53 expression as well as a Ki-67 LI above 20% (P < 0.01). Cox-2 and EGFR immunoreactive tumor cells showed a similar distribution pattern. Five-year survival rate was 73% in 57 cases showing higher Cox-2 expression and 100% in 14 cases showing lower expression, indicating a significant difference in survival (P = 0.040). Higher Cox-2 expression might be associated with tumor progression and worse prognosis through EGFR signaling interaction in Stage I bronchial adenocarcinomas.