In 1928, James Ewing challenged the "seed and soil" theory and proposed that metastasis occurs purely by anatomic and mechanical routes. This hypothesis has been recently utilized to suggest several hypotheses about the life cycle of circulating tumor cells (CTCs) and to postulate that the patterns of spread could be better understood through a 'filter and flow' perspective. However, contemporary evidences indicate that the primary tumour may dictate organotropic metastases by inducing the formation of pre-metastatic niches at distant sites, where incoming metastatic cells may engraft and colonise. Specifically, exosome vesicles secreted by tumours have been shown to home to pre-metastatic sites, where they activate pro-metastatic processes such as angiogenesis and modify the immune contexture, so as to foster a favourable microenvironment for secondary tumour growth.