The article reviews the history of the Wood of the Cross, from its reputed discovery in Jerusalem, its moves to Apamea, Constantinople and Rome, and the earliest traditions of circulating, presenting and venerating the relic in those cities. A study of the descriptions and dimensions of the various portions of the relic are used to support a number of hypotheses with regard to the relic's origins and movements. The application of scientific analyses are discussed. The article presents in a manner respectful of religious sensitivities to promote dialogue between religious institutions and scientific research.