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Despite multiple therapeutic advances, almost all people with multiple myeloma eventually become resistant to treatment and die of the disease. The lack of a potentially curative treatment means that myeloma has a tremendous personal and societal burden owing to shortened life expectancy, reduced quality of life and the cost of care. But multiple myeloma is always preceded by a premalignant condition, called monoclonal gammopathy of undetermined significance (MGUS), characterized by the presence of an abnormal monoclonal immunoglobulin protein in the blood, and sometimes by a precursor condition called smouldering multiple myeloma, that can be present for many years prior to diagnosis. Researchers now think that multiple myeloma is difficult to treat because physicians have conventionally delayed therapy until end-organ damage, which in myeloma consists of bone destruction, anaemia and renal failure, is detected. It is time to start systematically screening for, and treating, early-stage multiple myeloma in the groups of people at the highest risk, so that we can provide them with the best chance of long-term remission.