The Wood of the Cross upon which Jesus Christ was crucified is the greatest Christian relic of all. The history of its relics offers new insights into not only the development of the Christian world but also its scientific methods and concepts of materiality. Analyses are now available that permit us to obtain robust data from materials such as wood and bone. This can provide new historical information concerning the origins, circulation, and veneration of Christian relics. The present article sets out an approach to the integrated study of the Wood of the Cross, providing a general overview of the historical and material evidence and proposing suitable methods. These will be developed further as the authors’ research progresses.