The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile “soil”, where a “pre-metastatic niche” is established prior to future colonization by cancer cells. When the primary cancer progress from the confined disease to its invasive phase, tumor cells will acquire an invasive phenotype, enter into the circulation and colonize the previously prepared site where they will establish a “metastatic niche”. Among the variety of molecules that participate in the metastatic cascade, microRNAs are a class of small non-coding RNA that play an important role in the development of metastatic bone lesions. Many studies have addressed the role of small non-coding RNAs (miRs) in metastasis in osteotropic cancers and have highlighted the role of miRs as oncogenes (oncomiRs) or tumor suppressor miRs. In this review we present describe the role of miRs in the processing of the supportive bone microenvironment prior and after the bone colonization by cancer cells. Finally, future therapeutic strategies and perspectives are also discussed.