Cancer has typically been thought of as a linear disease, with metastasis occurring as a late event. However, a few studies suggest that cancer cell dissemination can occur very early in cancer progression. Now, Jean-Pierre Abastado and colleagues use a mouse melanoma model to show that immune cells infiltrate primary tumors and stimulate tumor cell dissemination, providing both a potential explanation for early metastatic phenotypes and a link between inflammation and cancer progression (PLoS Biol. 9, e1001162, 2011 ). The authors used RETAAD mice that carry an activated RET transgene and spontaneously develop uveal melanomas that eventually progress to cutaneous and visceral metastases. Previous studies have observed increased numbers of a specific subset of immune cells in the blood during tumor progression. Abastado and colleagues observed that these cells preferentially accumulated in primary tumors. The chemokines CXCL1, CXCL2 and CXCL5 were highly expressed in primary tumors and could attract PMN-MDSCs in vitro. Depleting mice of PMN-MDSCs showed that these cells favor primary tumor growth, and these mice also had fewer cutaneous metastases, demonstrating that these cells promote metastatic outgrowth. Finally, the authors showed that PMN-MDSCs induce epithelial-mesenchymal transition (EMT), a known hallmark of metastatic cells.