Metastasis is a rare event, in which most cancer cells cannot progress through major bottlenecks associated with invasion, intravasation, extravasation, seeding and colonization to produce a malignant macrometastatic tumour. In our laboratory, we use single cell technologies to investigate which kinds of cancer cells can metastasize and what unique properties enable them to do so. In this model, cancer cells are heterogeneous in genotype (nuclei) and phenotype (cytoplasm), and metastasis-initiating cells possess a distinct combination of both (Figure from Lawson, Kessenbrock et al., Nat Cell Biol, 2018). Dashed arrow indicates that cancer cells within micrometastases can die. Death rates within micrometastases can balance proliferation rates, and thereby prevent progression to macrometastasis by the failure to produce net positive growth.