Recent studies have challenged the previously postulated concept of a tumor-suppressive effect of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1). A possible angiogenic influence of CEACAM-1 in non-small-cell lung cancer (NSCLC) has not been investigated so far. Therefore, we examined microvessel density (MVD) and CEACAM-1 expression in primary NSCLC and analyzed their possible correlations under consideration of their prognostic effects. Specimens from 82 consecutive patients with completely resected NSCLC were stained immunohistochemically using the monoclonal anti-CEACAM-1 antibody 4D1/C2 and the monoclonal anti-CD31 antibody JC70A. The prognostic relevance of CEACAM-1 expression and MVD was evaluated by univariate Kaplan-Meier and multivariate Cox regression analysis. The median follow-up period was 75 months (range 10-156 months). A high MVD (i.e., > or =31microvessels/400x microscopic field) was observed more frequently in tumors with high CEACAM-1 expression (i.e., >/=66% stained tumor cells) than in tumors with low CEACAM-1 expression (61.8% vs. 33.3%, respectively; p=0.01). In univariate survival analyses, high CEACAM-1 expression and high MVD were associated with development of distant metastasis (p=0.011 and 0.022, respectively) and decreased cancer-related survival (p=0.046 and 0.006, respectively). Multivariate Cox regression analysis demonstrated that the prognostic impact of CEACAM-1 depended on the prognostic influence of MVD, while MVD itself represented an independent prognosticator for unfavorable cancer-related survival (p=0.021; relative risk 2.1; 95% confidence interval, 1.1-4.0). Here we show for the first time that high CEACAM-1 expression is associated with an increased angiogenic activity in NSCLC, and that the prognostic influence of CEACAM-1 might be derived from this association.