The aim of present investigation was to study the genetic instability in peripheral lymphocytes of lung cancer patients. The micronucleus (MN) assay and comet assay were simultaneously used to detect the spontaneous genetic change and ionizing irradiation (IR) induced genetic damage in peripheral lymphocytes from 36 lung cancer patients and 30 controls. In MN assay, the results of both two indicators, micronucleated cell frequency (MCF) and micronucleus frequency (MNF), indicated that the average values of MCF, MNF and IR-induced MCF, MNF of lung cancer patients were 9.25+/-0.58, 10.17+/-0.72, 66.14+/-2.07 and 75.64+/-2.34 per thousand, respectively, which were significantly higher than those (6.10+/-0.65, 6.60+/-0.74, 60.50+/-1.71 and 67.60+/-2.13 per thousand) of controls (P<0.05 or 0.01). In comet assay, the results of mean tail moment (MTM) and IR-MTM showed 0.84+/-0.07 and 1.09+/-0.11, respectively, which were significantly higher than those (0.60+/-0.05 and 0.70+/-0.10) of controls (P<0.05). However, the difference between lung cancer group and control group for the mean tail length (MTL) and IR-MTL was not significant (P>0.05). The results of present investigation indicated that the genetic instability in peripheral lymphocytes of 36 lung cancer patients was significantly higher than that of controls.