Purpose of the review <p>Breast and pancreatic cancers are among the most insistent malignancies, characterized by high metastatic potential and limited long-term survival, particularly in the case of pancreatic ductal adenocarcinoma (PDAC). Emerging evidence highlights the pivotal role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as key regulators of tumor progression, epithelial–mesenchymal transition (EMT), angiogenesis, and metastasis.</p> Findings <p>These molecules function through complex mechanisms such as post-transcriptional gene regulation, epigenetic remodeling, and competing endogenous RNA (ceRNA) networks, influencing critical oncogenic pathways like PI3K/AKT, Wnt/β-catenin, and TGF-β. In breast cancer, ncRNAs modulate tumor subtype behavior, therapy resistance, and metastatic organotropism, while in pancreatic cancer, they contribute to desmoplastic remodeling, immune evasion, and chemoresistance. Importantly, the stability and detectability of circulating ncRNAs in biofluids position them as promising non-invasive biomarkers for early diagnosis, disease monitoring, and treatment stratification.</p> Summary <p>This review consolidates current knowledge on the roles of ncRNAs in the progression and metastasis of breast and pancreatic cancers, explores their clinical biomarker potential, and discusses the therapeutic opportunities and challenges associated with ncRNA targeting. Understanding the dynamic regulatory roles of ncRNAs may pave the way for more precise, RNA-based diagnostics and therapeutics in these deadly cancers.</p>