This article examines Block A, the first block-style building in Heybeliada Sanatorium in Istanbul. The purpose of this research is to understand its architectural and spatial development and discuss how in fact it was a “prototype” of Turkish sanatoria. Approached with a three-step methodology (documentation/evaluation/results) this research conducts architectural and spatial analysis on Block A. Primary sources like architectural documentation and restitution drawings, the writings of the institution’s head doctor Tevfik Ismail Gökçe, periodicals on tuberculosis (TB), as well as pertinent literature are utilized. The findings demonstrate that Block A’s development (1924—1945) was the result of knowledge transfer that introduced the universal sanatorium design principles, spatial experiments, adaptation to sociocultural norms, and trial-and-error processes. Not only it had a major impact on shaping of the second block-type building in the complex, the “model” Block B, but it also became exemplary of the subsequent Turkish sanatoria. The originality of this article is its exploration of the changing and evolving Block A in its resonation with the cultural tensions of Turkey’s modernization process. This was established via the assessment of budgetary issues, medical developments and climatic experiments, the social issue of scarcity of TB beds in the country, spatial practices to separate the sexes as reflections of local traditions and culture in the shaping of spaces.