EGFR mutations have been shown to correlate with the clinical responsiveness to epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI). The detection of EGFR mutations in non-small cell lung cancer (NSCLC) is important from the perspective of targeted anticancer therapy. We report the first case showing that the status of EGFR mutations can be successfully determined in malignant pleural effusion of NSCLC using polymerase chain reaction (PCR) technique, and correlated to the clinical responsiveness to gefitinib, an EGFR-TKI. This case demonstrated the importance of molecular cytology in the era of targeted therapy.(c) 2005 Elsevier Ireland Ltd. All rights reserved.