MicroRNAs (miRNAs) are a family of highly conserved noncoding single-stranded RNA molecules of 21 to 25 nucleotides. miRNAs silence their cognate target genes at the post-transcriptional level and have been shown to have important roles in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. Recent evidence indicates that the expression of miR-181a is altered in breast tumor tissue and in the serum of patients with breast cancer. However, there are several contradicting findings that challenge the biological significance of miR-181a in tumor development and metastasis. In fact, some studies have implicated miR-181a in regulating breast cancer gene expression. Here we summarize the current literature demonstrating established links between miR-181a and human breast cancer with a focus on recently identified mechanisms of action. This review also aims to explore the potential of miR-181a as a diagnostic and/or prognostic biomarker for breast cancer and to discuss the contradicting data regarding its targeting therapeutics and the associated challenges.