Malignant cells express molecular pathways that are also expressed by myeloid cells. Such behaviour is associated with loss of homotypic adhesion between cells, changes in the cellular matrix, induction of angiogenesis, motility, chemotaxis, and several immune-signalling pathways. The overlap between malignant cells and myeloid cells could be explained by one mechanism: fusion of myeloid cells and tumour cells, as noted in animal studies and in two patients with renal-cell carcinoma who underwent bone-marrow transplantation. An overlapping trait in these cells is their glycosylation patterns: hybrids have high expression of N-terminal glycosylation and beta1,6-branched oligosaccharides. In macrophages and cancer cells, these structures have a role in motility and systemic migration; in cancer, they are associated with metastasis and poor prognosis. In addition to myeloid traits, fusion might contribute to aneuploidy and plasticity in cancer. Understanding metastatic cells as myeloid-tumour hybrids suggests new strategies for diagnosis, treatment, and prevention of malignant disease.