Cancer is the result of complex processes that involve multiple molecular alterations. The understanding of such complexity has been improved by the advent of a new class of small, noncoding RNA gene products known as microRNAs (or miRNAs). miRNAs play an essential role in cancer development and progression by modulating gene expression binding to target mRNA, causing either mRNA degradation or translation inhibition. Several studies have shown that miRNAs can act either as tumor suppressors or as oncogenes, and that measurement of miRNA expression in malignancies may have diagnostic and prognostic implications. Beyond these valuable features, miRNAs could be potentially used in the future as innovative and targeted therapeutics. Recent in vitro and expression profiling studies have identified that specific miRNAs are directly involved in brain carcinogenesis and in the metastatic process. This review focuses on metastasis-related miRNAs and on the role of miRNAs in distinguishing between primary and metastatic brain tumors. In clinical practice, miRNAs could represent a promising new class of cancer biomarkers in the diagnosis and management of brain neoplastic lesions.