OBJECTIVE To prove the hypothesis that there may be different tumor suppressor genes (TSGs) involved in genesis of squamous cell carcinoma (SCC) and adenocarcinoma (ADC) in non-small cell lung cancer (NSCLC) in the Chinese. METHODS Twenty-two microsatellite markers flanking to or within 13 identified or candidate TSGs were used to detect loss of heterozygosity (LOH) in these regions in the specimens of 28 SCC patients and 13 ADC patients. RESULTS Our data demonstrated frequent allelic loss of FHIT, p53, IFNA, VHL and p16 both in SCC and ADC. Three genes, PRLTS, PTEN and p57, showed statistically significant differences in the LOH frequency between SCC and ADC. CONCLUSION The comparison of LOH frequencies between SCC and ADC indicates possible correlation between specific tumor suppressor genes and each type of lung cancer. The results also suggest that more attention should be paid to the PRLTS gene, which may play an important role in the development of ADC.