For solid tumours to grow, they must gain access to a blood supply and until recently tumour vascularization was thought to arise solely via endothelial cell proliferation (angiogenesis). There is increasing evidence for cancer cells to form vascular structures (vasculogenic mimicry, VM) and as with angiogenesis, increased VM correlates with poor outcome for cancer patients. Increased circulating platelet counts also correlate with poor outcome for cancer patients and platelets are predicted to be pro-angiogenic; whether platelets are pro-VM is unknown. This study provides several novel insights into the role of platelets in cancer. First, we reveal with in vitro assays that platelets do not influence angiogenesis, but they do actively inhibit VM by human breast cancer and melanoma cells. We also demonstrate that both platelet sized beads and the releasates from platelets were partially effective at inhibiting VM formation. Further in vitro analysis reveals that platelets promote cancer cell migration. In an in vivo model of MDA-MB-231-LM2 breast cancer, low-dose aspirin perturbed cancer burden. This low-dose aspirin did not significantly influence metastasis, neutrophil content, angiogenesis or VM, but did increase necrosis and alter gene expression by the cancer cells. Taken together, this study provides new insights into the role of platelets in VM, aspirin and cancer progression.