The antigenic structure of Treponema pallidum was described in the 1940s and 1950s. The main contributions of Giuseppe D'Alessandro and his collaborators included the description of the external membrane and of the polysaccharide antigen found in the cell wall of the microorganism. Based on new knowledge it has been possible to develop diagnostic tests that are more sensitive and specific than nontreponemal tests, which nevertheless retain their validity in the current re-emergence of syphilis as a public health problem.