Since the mortality of lung cancer patients remains very high, the development of a sensitive detection method remains an urgent task. The authors have designed common melanoma antigen gene (MAGE) primers that enable the detection of MAGE A1 to A6 subtypes simultaneously. These primers were applied to the detection of lung cancer using sputum specimens. The study involved, 53 cancer patients and three non-cancer groups (193 healthy people, 235 lung cancer screening group and 140 patients with benign lung diseases) were investigated. One hundred and thirty-six respiratory specimens (55 random sputa, 33 induced sputa, 40 broncho-alveolar lavage (BAL) fluids, and 8 pleural fluids) from different lung cancer patients were blindly tested. The MAGE assay was performed by RT-nested PCR, and the results obtained from sputum were compared with those obtained by telomerase assay and conventional cytology. In the sputum of the non-cancer groups, the positive rates were less than 2.1%, while the detection rates were 83.3% in the cancer tissues and 54.3% in the sputa of lung cancer patients. For the random sputum samples of lung cancer patients, the detection rate was 47.5%, but in the induced sputum, BAL and pleural fluids, the detection rate was up to over 70.0%. The MAGE assay produced a higher detection rate than the telomerase assay and conventional cytology. MAGE A1-6 RT-PCR, which showed high sensitivity and specificity, provides an effective means for the lung cancer detection in sputum.