Targeting chemokine (C-C motif) ligand 2 (CCL2) paracrine signalling from tumour cells to monocytes has been shown to inhibit metastasis. Using four syngeneic mouse models of metastatic breast cancer, Bonapace et al. showed that cessation of CCL2 inhibition increased cancer cell dissemination and monocyte release from the bone marrow, leading to increased metastasis and decreased survival. Importantly, combined inhibition of CCL2 and interleukin-6 (IL-6) reduced metastasis and improved survival. As CCL2 inhibition is being developed for anticancer therapy, this paper identifies the need for caution and a clearer understanding of targeting the tumour microenvironment.