<p>The calcium-sensing receptor (CaSR) plays a crucial role in cellular signaling and has been implicated in cancer progression. However, its specific role in breast cancer remains unclear. This study aimed to investigate CaSR gene expression levels, its correlation with oncogenic pathways, and its protein localization in human breast cancer tissues.</p><p>Quantitative real-time PCR (qRT-PCR) was used to analyze the relative expression of CaSR and associated genes in malignant and adjacent non-malignant breast cancer tissue samples. Pearson correlation analysis was performed to assess relationships between CaSR and other oncogenic markers. Immunohistochemistry (IHC) was conducted to evaluate CaSR protein localization and intensity in different breast cancer grades and fibroadenoma tissues.</p><p>Our findings revealed that 56% of patients exhibited elevated CaSR expression, with significant positive correlations between CaSR and oncogenic genes such as HOTAIR, SNOR78, BC200, DSG1, DSC1, HER2, BRCA1, p38 MAPK, and Akt (<i>p</i> = 0.001 for most correlations). Additionally, CaSR expression negatively correlated with menopausal status (<i>p</i> = 0.001), suggesting hormonal influences on its regulation. IHC analysis showed strong membranous and cytoplasmic staining in grade II tumors without metastasis (+ 3) but weak or undetectable CaSR expression in advanced metastatic cases. These findings indicate a potential role for CaSR in tumor progression, adhesion, and metastasis.</p><p>Importantly, this study provides novel evidence linking CaSR expression to non-coding RNAs, desmosomal adhesion molecules, and MAPK/AKT signaling pathways, highlighting previously unexplored mechanisms through which CaSR may influence breast cancer progression and metastatic behavior. Further research is needed to determine its potential as a biomarker or therapeutic target in breast cancer treatment.</p>