The De humani corporis fabrica [The Fabric of the Human Body], Basle, 1543, of Andreas Vesalius is deservedly famous as the first modern book of anatomy. A second edition was published in Basle in 1555, but little is known of Vesalius’ activities after that date. This article discusses a recent find: Vesalius’ own copy of the 1555 edition, heavily annotated in preparation for a never published third edition. Vesalius made hundreds of changes to the second edition, the great majority being stylistic, altering the Latin words but not the overall meaning. There are also changes to the plates to give greater clarity or to correct mistakes by the original block-cutter. There is little new anatomical material, although Vesalius continued to meditate about what he had earlier discovered. He shows no sign of being acquainted with the findings of others, like Colombo or Falloppia, that were published after he had moved his residence from Brussels to Spain in summer 1559, perhaps leaving this volume behind. The number of annotations shows Vesalius’ passionate concern not only for accuracy but also for the most effective way of proclaiming his new anatomical message.