Theories of medical diagnosis have been debated since at least the early eighteenth century. They were closely linked to different understandings of health and disease. In general, naturalistic and ontological understandings were confronted with nominalistic and constructivist interpretations of signs and symptoms. The foundations of today’s understanding of diagnosis were laid in the nineteenth century, which brought new ideas about the differentiation of individual diseases. The article reconstructs this development of concepts of medical diagnosis and discussions about the production of diagnostic signs. It then presents two approaches from the 1920s that attempted to reconcile nominalism and essentialism. The focus is on the approaches of the physicians Richard Koch and Francis Crookshank. Their concepts are compared and linked to Hans Vaihinger’s As-If philosophy, which was very prominent at the beginning of the twentieth century. The paper argues that Koch, in particular, sought to give an intentional and relational orientation to the idea of diagnosis, seeing nature and culture in diagnosis not as opposites but as interrelated elements, and that Koch’s and Vaihinger’s approaches still offer much insight into contemporary thinking about the theory of diagnosis.