The factors conferring the increased malignancy on lung adenocarcinoma with micropapillary component (AC-MPC) remain to be elucidated. On proteomics based on 2-dimensional gel electrophoresis, 19 proteins differentially expressed by more than 1.5-fold between AC-MPC and conventional adenocarcinoma (CAC); in particular, vimentin, one of the proteins, was 3.5-fold up-regulated in AC-MPC. Subsequent semi-quantitative investigation by immunohistochemistry with large cohorts comprised 101 AC-MPC and 119 CAC, respectively, of different stages revealed that vimentin was expressed in MPC of 95 (94.1%) AC-MPC and the expression scores were higher than those of well- and moderately differentiated CAC, as well as the background non-MPC of the AC-MPC (P< 0.0001), but not significantly different from those of poorly differentiated CAC (P= 0.561). Even within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis (P< 0.02), and multivariate analysis showed that high vimentin expression and worse node statuses were independent indicators of adverse prognosis (P< 0.048). In conclusion, vimentin expression is prevalent and markedly up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.