Tumour growth and spread requires an adequate supply of oxygen and nutrients which is provided by complex blood structures of the tumour vasculature. Circulation of the blood through a tumour can occur via angiogenesis which has been successfully targeted by anti-angiogenic inhibitors. However, these anti-angiogenic strategies have revealed adaptive processes by cancer with high levels of plasticity and aggressiveness evolving and the formation of vasculogenic mimicry (VM) to provide additional access by the tumour to the blood supply. This adaptation allows cancer cells themselves to form vascular-like channels, thus creating new dynamic ways to spread and metastasise which have documented significant and detrimental impact on patient survival. This process has been described in invasive ductal breast carcinoma (IDC) which is a highly vascularised and aggressive cancer. We have previously shown that interleukin-3 (IL-3) is pro-angiogenic and now reveal that it is also intimately involved in the VM process by breast cancer cells. In fact, we observed that IL-3 promotes the acquisition of a VM gene profile and VM formation by human IDC cells lines as well as the activation of VM signalling pathways such as PI3K/Akt and MAPK. In addition, we observed an increase in VM markers (VE-cadherin and laminin) as well as epithelial mesenchymal transition (EMT) markers related to cancer cell plasticity and metastasis. Interestingly, we also found that IL-3 has indirect paracrine effects leading to (i) an increase of anoikis resistance, (ii) an increase in invasion by the breast cancer lines and (iii) an enhanced ability to promote EMT in surrounding breast cancer cell lines. We have identified chemokines released by IL-3 stimulated VM competent breast cancer cells that are related to these paracrine effects. Taken together, our results suggest that, in addition to being pro-angiogenic, IL-3 promotes VM by breast cancer cell lines which causes tumour spread via increased cancer cell survival, migration, invasion and EMT within the local microenvironment. The identification of IL-3 as a single pro-tumourogenic factor that is able of promoting both angiogenesis and VM provides a unique opportunity to target one single hormone to actively inhibit in the most aggressive breast cancers.