Metastatic tumor antigen 2 (MTA2) is a member of the MTA family that is closely associated with tumor progression and metastasis. In this study, the expression profile of MTA2 in 223 cases of non-small cell lung cancer (NSCLC) tissues and two lung cancer cell lines was investigated. Interestingly, we found MTA2, which was believed to have nuclear distribution only, was distributed in both nucleus and cytoplasm in normal and cancer cells. Nuclear MTA2 expression was detected in 148 cases of NSCLC (66.4%), and was correlated with advanced TNM stages (p=0.023), tumor size (p=0.036), and lymph node metastasis (p=0.004). Besides, the Ki-67 proliferation index was significantly higher in nuclear MTA2-positive tumors than in nuclear MTA2-negative tumors (r=0.538, p=0.006). However, there was no significant difference in cytoplasmic MTA2 status by age, gender, tumor stage, histology, grade, lymph node metastasis, and Ki-67 proliferation index. Univariate analysis revealed nuclear MTA2 expression was correlated with poor overall survival (p=0.035), whereas there was a nonsignificant trend in the same direction for cytoplasmic MTA2 (p=0.134). Multivariate Cox regression analysis revealed the overexpression of nuclear and cytoplasmic MTA2 not to be independent factors predictive of poor disease outcome. Our data suggested that MTA2 might play roles in both the nucleus and cytoplasm in the progression of NSCLC.