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Objective: Biological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung cancer (NSCLC) treated with gefitinib are urgently needed.Methods: We analyzed EGFR / HER2 / HER3 primary tumour immunohistochemical expression in a prospective and consecutive series of 90 Chinese patients.Platinumpretreated patients received a 250 mg oral dose of gefitinib once daily until disease progression; EGFR / HER2 / HER3 tumour status was related with the clinical outcome in terms of response rate (RR), time to disease progression (TTP), and overall survival (OS).Results: A high expression (scores 2-3) of EGFR, HER2 and HER3 was verified in 16.7%, 43.3% and 21.1% of tumors, respectively.EGFR and HER3 status were not significantly related with response, while the HER2 overexpression result was significantly associated with a higher RR (35.9% vs.15.7%, P = 0.027).The RR in the 13 patients with both HER2 and HER3 expression was also significantly higher than in the other 77 patients (53.8% vs.22.1%, P = 0.036).EGFR / HER2 / HER3 status was not significantly correlated with TrP or OS.Conclusion: The HER2 immunohistochemical expression can play a role in the clinical management of Chinese patients with advanced NSCLC who are candidates for gefitinib therapy