This Working Group paper looked at chemical technology and epistemological debate in the works of Leonardo da Vinci and Vannoccio Biringuccio. During the Renaissance the field of the chemical arts was characterised by the complex identity of its protagonists, who would hardly recognize themselves in the traditional socio-cultural and professional categories. Although it is anachronistic to speak of chemistry as a discipline, during the late fifteenth and early sixteenth century, it is possible to outline an area of interest around the transformation processes of substances in which various fields of theoretical and practical knowledge intersect. In this cultural context the figures of Leonardo da Vinci and Vannoccio Biringuccio distinguish themselves as they, in addition to their experimental activity, became the promoters of a general reform of chemical arts and natural philosophy. Both authors reject transmutational alchemy that did not respect the criteria of rational and empirical verification but, at the same time, they praise it for discovering new substances and innovative technological processes. Leonardo and Biringuccio go beyond the operational dimension of chemical arts to take into account the structure of matter and the dynamics of chemical-physical phenomena such as the generation of minerals and interactions among the natural elements. Leonardo, even if his writings are fragmentary and unsystematic, has the merit of illustrating and describing, both traditional and experimental processes and chemical-metallurgical equipment, sometimes for the very first time. Biringuccio, about 30 years later, writes a compendium in which he gathers all the arts of fire, including alchemy and creates the first organic treatise of what might carefully be called "empirical chemistry."