Treatment failure for lung adenocarcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate the invasion- and metastasis-related gene, neural precursor cell expressed, developmentally downregulated 9 (NEDD9), in lung adenocarcinoma tissues and cell lines. The expression of NEDD9 was analyzed by the SP method of immunohistochemistry for 60 formalin-fixed and paraffin-embedded (FFPE) lung adenocarcinoma tissues in which 32 cases were metastastic and 28 were without metastases. NEDD9 mRNA expression and protein levels were quantified by fluorescence quantitative reverse transcription-polymerase chain reaction (FQ-PCR) and western blotting in the highly invasive lung adenocarcinoma cell lines A549 and 95D as well as in SPC-A-1 cells with low invasive potential. The immunostaining scores revealed a statistically significant difference between metastatic and non-metastatic lung adenocarcinomas (p<0.001). FQ-PCR and western blotting demonstrated that NEDD9 expression was higher in A549 and 95D compared to SPC-A-1 cells (P=0.003). Our results provide evidence that NEDD9 is upregulated in metastatic lung adenocarcinoma and in highly invasive lung adenocarcinoma cell lines, suggesting its potential involvement in regulating cell migration and invasion.