Cancer is a multistep genetic process that occurs when a cancer cell divides. Knowledge of the steps and errors in our genomic book, leading to cancer, is fascinating, but still incomplete. The biological ‘Holy Grail’ would be to know the very first event leading to the inexorable progression of a normal cell to a malignant cell, and then to a malignant tumour. One clue lies in the genes involved in hereditary predisposition to cancer, since the very early embryo can be considered as genetically normal, except for one inherited mutated gene, which will lead to an increased risk of cancer, sometimes decades later in the person’s life. This is a fruitful quest, but the ‘Holy Grail’ is still hidden in a more complex cancer process, involving the effects of mutations in possibly multiple genes with or without environmental factors, which may be interacting. Nevertheless, the genesis and biology of a tumour cell is now better understood, largely due to the study of the function of cancer predisposition genes. This will also provide new hope for innovative molecular therapeutic tools.