Anti-Factor VIII vessel immunostaining has been widely used in the detection of angiogenesis in non-small cell lung cancer and other tumors. Several new antibodies have shown a higher sensitivity, and anti-CD31 has recently been proposed to be the standard for microvessel study. In the present study, we comparatively evaluated the two antibodies in 134 cases of early operable non-small cell lung cancer. The F8/86 (anti-Factor VIII-associated antigen) and JC70 (anti-CD31) MoAbs were used in paraffin-embedded material. Eye appraisal of vascular grade (VG) and microvessel score (MS) was performed by three experienced pathologists. Different cutoff points were used for the analysis of VG and MS correlation with nodal involvement, overall survival, and thymidine phosphorylase expression. Intra- and interobserver variability was minimal for both antibodies. MS and VG were significantly correlated with each other. However, 54 and 22% of cases with high anti-CD31 VG or high MS, respectively, had low vascularization on anti-Factor VIII assessment. Anti-CD31 scoring was significantly associated with nodal involvement and overall survival for all cutoff points considered, which was not verified for anti-Factor VIII staining. VG was the most significant indicator of nodal involvement and survival for both antibodies. Tumors with high VG by anti-CD31 but low or medium VG by anti-Factor VIII behaved as tumors of high neoangiogenesis, defining a poor prognosis (P = 0.005) despite the failure of anti-factor VIII antibody to highlight intense neoangiogenesis. Anti-CD31 MS significantly associated with thymidine phosphorylase overexpression (P = 0.01), whereas no correlation was found for anti-Factor VIII counting. It was concluded that anti-CD31 microvessel immunostaining has several advantages over anti-Factor VIII, being a more sensitive method for highlighting small, immature microvessels or single endothelial cells. This could be of importance in revealing possible correlation of tumor angiogenesis with metastatic behavior, prognosis, or angiogenic factor overexpression. Vascular grading was the best method for neovascularization assessment, efficiently defining groups of tumors with aggressive clinical course.