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The ancient physician Hippocrates described the projection of blood vessels from a collection of cells as ‘karkinos’, the Greek word for crab. Today, we know this malignant growth as cancer. Although it remains one of our biggest killers, survival rates for several tumour types have improved dramatically in recent years. These Milestones celebrate two decades of breakthroughs in basic, translational and clinical research which have revolutionised our understanding and management of cancer.