Malignant pleural effusions (MPEs) are often observed in lung cancer, especially adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in lung adenocarcinoma. The purpose of the present study was to investigate the EGFR mutation rate in MPEs of lung adenocarcinoma. Between June 2005 and December 2006, 136 MPEs from lung adenocarcinoma were collected for EGFR mutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of lung adenocarcinoma from patients without MPEs were assessed for EGFR mutation. The EGFR mutation rate was significantly higher in the patients with MPEs than in the patients without (68.4% versus 50.5%). The EGFR mutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0-1, and EGFR mutation were significantly associated with a longer overall survival for lung adenocarcinoma patients with MPEs. The patients with malignant pleural effusions related to lung adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for lung adenocarcinoma with malignant pleural effusions in east Asia.