The main aim of this study was to explore the molecular structural relationship between annexin II (ANXA2) and Lewis y antigen by determining their expression patterns and clinical significance in ovarian epithelial carcinoma. The structural relationship between ANXA2 and Lewis y antigen was examined using immunoprecipitation and confocal laser scanning microscopy in two ovarian caner cell lines ES-2 and CaoV-3. We also constracted the stably transfected cell lines with low ANXA2 gene expression in order to detect the expression level between ANXA2 and Lewis y. ANXA2 and Lewis y were detected in tissues from malignant, borderline, benign, and normal ovarian tissues using immunohistochemical analysis. ANXA2 and Lewis y were present in both two ovarian cancer cells and ANXA2 contained Lewis y antigen. Moreover, expression of Lewis y antigen in ANXA2 from cell after transfection was higher than that before. Our immunohistochemistry data revealed significantly higher positive expression rates of ANXA2 in malignant ovarian tissues, compared to benign tumor and normal tissue, similar to Lewis y antigen levels in ovarian cancer. Notably, tissues displaying marked expression of ANXA2 simultaneously expressed high levels of Lewis y antigen. A linear correlation between the expression patterns of ANXA2 and Lewis y antigen was evident. Consistently, double-labeling immunofluorescence experiments illustrated co-localization of ANXA2 and Lewis y antigen within the same area. In conclusions, ANXA2 contains Lewis y antigen. Our results further demonstrate a close correlation between the expression levels of the two antigens, which are significantly high in ovarian cancer.