Mary Lyon, who has died aged 89, was one of the foremost geneticists of the 20th century. She used the mouse as a powerful genetic tool to gain fundamental and profound insights into mammalian genetics and the genetic bases of disease. Perhaps her greatest achievement was to propose in 1961 the theory of X chromosome inactivation, in which she suggested that one of the two X chromosomes in the cells of female mammals is randomly inactivated during early development. This process is now sometimes referred to as Lyonisation, and the theory has had a fundamental impact on research into mammali