The current study was undertaken to compare the usefulness of hemotoxylin and eosin (H&E) staining and immunohistochemical staining to identify lymphovascular space invasion (LVSI) in endometrial cancer and to evaluate the presence of LVSI detected by either technique as an independent prognostic factor. Histologic sections from 92 patients with clinical stage I-II endometrial cancer were reviewed, and representative sections were stained immunohistochemically with antibodies for von Willebrand factor and blood group isoantigens. To compare the prognostic significance of LVSI detected by H&E staining with that detected by immunohistochemical staining, univariate and multivariate analyses were performed. Thirty (32.6%) of the 92 cases showed LVSI in H&E staining. In 8 of the 30 cases, LVSI was negative by immunohistochemical staining, while LVSI was positive by immunohistochemical stainings in 2 of 62 cases showing negative LVSI in H&E staining. In univariate analysis, LVSI detected by H&E and immunohistochemical staining was proved to be significant as a prognostic factor. In multivariate analysis by Cox's proportional hazards model, LVSI identified by H&E staining was selected as one of significant prognostic factors, but LVSI identified by immunohistochemical staining not selected. The results of this study indicate that LVSI is one of the independent prognostic factors in endometrial cancer, and that LVSI as detected by H&E is more prognostic of survival than immunohistochemical detection.