Breast cancer (BC), a prevalent malignancy among women, is a global cause of cancer-related mortality 1, 2. With an incidence rate of 10%, BC particularly affects under the age of 45 [3]. Various genetic changes and other factors related to lifestyle have an impact on the development and progression of BC 4, 5. Primarily, BC is categorized into four molecular subtypes including HER2-overexpressing, luminal A, luminal B, and basal, with different clinical courses, prognoses, and treatment strategies 6, 7, 8. The underlying molecular mechanisms of BC are mainly classified into five subtypes based on the expression of specific receptors: human epidermal growth factor, estrogen, and progesterone. This classification helps predict patient outcomes and select the most appropriate treatment options [9]. Genomic instabilities, such as BRCA1 and BRCA2 mutations, are among the main causes of BC 9, 10, 11. Numerous studies have been conducted to identify potential biomarkers for early and efficient diagnosis of BC 12, 13. Recently, there has been a growing interest in the application of novel sequencing technologies 14, 15. Preliminary data propose that regulation of non-coding RNAs (ncRNAs) can lead to substantial anti-cancer features [16]. Piwi-interacting RNAs (piRNAs), measuring 25-30 nucleotides long, originate from repetitive intergenic fragments in the genome, known as piRNA clusters, and are predominantly found in mammalian embryonic germ cells [17]. Based on their source, piRNAs are categorized into three types: piRNAs derived from transposons, those originating from lncRNAs, and those that are derived from mRNAs 18, 19, 20. Additionally, piRNAs are divided into two sub-groups: pre-pachytene piRNAs, which operate in premeiotic germ cells, and pachytene piRNAs, which are involved in meiosis and the haploid spermatid phase [21]. While both types of piRNAs share the same molecular characteristics, the cluster of pre-pachytene piRNAs is distinct and contains repetitive sequences. The primary function of piRNAs is to preserve genome integrity by suppressing transposons [22]. The growth and homeostasis of organisms are precisely controlled by regulating gene expression, which is conducted by RNA silencing. Besides, piRNAs have a significant impact on physiological procedures at the transcriptional and post-transcriptional stages 23, 24. RNA-induced silencing complex (RISC), a ribonucleoprotein silencing compound, is formed when piRNA combines with PIWI proteins [25]. This complex is vital to preserving integrity transposon silencing, epigenetic regulation and rearrangement of genome, protein modulation, spermiogenesis, and formation of heterochromatins [26]. Recent research has found abnormal expression of piRNA and PIWI proteins in various cancers, including BC [27]. An elevated expression of piRNAs and PIWI proteins has been proposed to be associated with the development and prognosis of various human tumors 27, 28. Unlike miRNAs, piRNAs often do not match the mRNA of target genes, highlighting that their function is mainly conducted through epigenetic modulation of biological functions, specifically in cancer [29]. piRNAs can represent oncogenic and/or tumor-suppressive properties [30]. Epigenetic changes, such as histone hypoacetylation and DNA hypomethylation, can silence tumor suppressors and activate oncogenes 31, 32. A select group of genes in healthy cells are epigenetically modulated by piRNAs, leading to the identification of tissue-specific signatures regarding the expressed piRNAs [33]. It has been reported that the expression of piRNA varies meaningfully across human somatic cells, with varying grades of heterogeneity in different tissue types 34, 35. Despite the fact that most piRNAs are encoded in the human germline, only a few are steadily expressed in both tumor and normal tissues [36]. Abnormal piRNA expression is potentially a cancer-specific markers that can be related to the clinical manifestations of cancer, emphasizing their importance in the early detection of cancer [37]. The role of piRNA and PIWIs as prognostic and diagnostic biomarkers of BC is mainly due to their potential to induce tumorigenesis, invasion, progression, and metastasis of cancer cells while suppressing cellular apoptosis. These finding further introduce piRNA as potential tools in the prognostic and early diagnostic of BC 22, 38. The aberrantly expressed piRNAs are suggested to have the capacity to be utilized as biomarkers and/or therapeutic agents in BC [22]. Herein, we aim to provide a comprehensive overview of the biogenesis, maturation, and biological function of piRNA and their significant role in malignancies with a specific focus on BC. The main role of piRNA s in BC are discussed in detail. In addition, the importance of piRNAs as BC biomarkers and their potential in BC treatment are highlighted.