Background <p>Breast cancer (BC) accounts for approximately one-third of Cancer cases. It is responsible for nearly 16% of all cancer-related deaths among females. Increasing incidence and high mortality associated with BC has prompted the researchers to investigate the genetic and epigenetic mechanisms of the disease.</p> Aim <p>This study aims to clarify the epigenetic role of lncRNAs: A2M-AS1, DBH-AS1 and NCBP2-AS2.</p> Materials and methods <p>This case-control study was conducted on fifty patients with BC. A complete medical history, clinical examination, investigations (including mammography and tumor markers), and gene expression analysis were performed. Tumor and adjacent normal breast tissue samples were obtained from patients who underwent mastectomy, used for RNA extraction and gene expression levels of A2M-AS1, DBH-AS1, and NCBP2-AS2 were quantified using PCR.</p> Results <p>Each of A2M-AS1, DBH-AS1 and NCBP2-AS2 is significantly overexpressed in tumor cases indicating their involvement in BC etiopathogenesis (P value &lt; 0.001). However, unlike A2M-AS1 and DBH-AS1, NCBP2-AS2 is not significantly associated with clinicopathological characteristics of BC (P value ranging from 0.082. to 0.877). A2M-AS1 and DBH-AS1 are significantly associated with metastatic progressed BC cases P value ranging from (0.001 to 0.025).A2M-AS1 is significantly overexpressed in breast with elevated CA125-3 (P value = 0.030).</p> Conclusion <p>A2M-AS1, DBH-AS1, and NCBP2-AS2 lncRNAs are significantly overexpressed in BC. A2M-AS1 and DBH-AS1 overexpressed in metastatic and progressed cases, while A2M-AS1 is significantly elevated in cases with high CA125-3 levels. Additionally, DBH-AS1 may indirectly regulate NCBP2-AS2.</p>