The objective of this study is to better understand the molecular mechanism of tumor invasion and metastasis, and isolating tumor metastasis-related genes. Two human lung adenocarcinoma cell lines AGZY-83a and Anip973 were studied. Anip973 was derived from AGZY-83a, but it manifested a very much higher metastatic potential than the parent line. Differential cDNA fragments were isolated by using the techniques of mRNA differential display, and analyzed by means of molecular cloning and sequencing. The expression of RAB5A gene in clinical samples of non-small cell lung cancer was determined by RT-PCR. There were significant differences between AGZY-83a and Anip973 in gene expression. Part of the differential cDNA fragments were cloned and sequenced. We found that there was over-expression of RAB5A gene in the Anip973 cell line. And there was over-expression of RAB5A gene in those samples of clinical lung cancer showing metastasis. In conclusion, the expression or over-expression of RAB5A gene was associated with the metastatic phenotype of Anip973. Probably, over-expression of RAB5A gene in non-small lung cancer may serve as a diagnostic marker for metastasis.