Backgroundβ-Catenin mediates cellular adhesion and the Wnt/β-catenin signaling mechanism, thereby controlling cell proliferation and differentiation. Studies of endometrial tissue suggest that there are differences in β-catenin expression during the course of regular menstrual cycles. However, differences in expression in squamous epithelial cells between the proliferative and secretory phases have hitherto remained unknown. ObjectivesTo localize β-catenin in squamous epithelial cells in cervicovaginal smears during the course of regular menstrual cycles. MethodsIn this observational study, smears were taken from women (n = 102) with various gynecological complaints. Squamous epithelial cells were stained using a Papanicolaou method to evaluate their cytology and any infection. An anti-β-catenin antibody was used to localize immunoreactivity in the cell membrane, cytoplasm, and/or nucleus. ResultsWomen with a regular menstrual cycle (n = 62) were divided into 2 groups: those in a proliferative phase (26/62, 42%) and those in a secretory phase (36/62, 58%). Cytoplasmic and nuclear β-catenin immunoreactivity was observed prominently in the proliferative phase (19/26, 73%), whereas low-level β-catenin immunoreactivity was seen in the secretory phase (9/36, 25%). Compared with the secretory phase, the mean H-scores for β-catenin immunoreactivity in the proliferative phase were significantly increased in the membrane (P = 0.039), the cytoplasm (P < 0.001), and the nucleus (P = 0.033). By contrast, β-catenin immunoreactivity was reduced from parabasal to superficial cells in both the proliferative and secretory phases. ConclusionsCytoplasmic and/or nuclear β-catenin immunoreactivity may indicate that the activity of the Wnt/β-catenin signaling pathway is cycle dependent.