The Instituto de Botánica Darwinion (CONICET and ANCEFyN) was founded by the end of 1910 in the San Martín district by Cristóbal María Hicken as his private botanical research laboratory. Its name honors Charles Darwin for his brilliant theory of biological evolution. In 1924, Cristóbal M. Hicken made public his desire to bequeath the Instituto de Botánica Darwinion to the National State, a fact that only materialized in 1934. But in the early ‘30s, he decided to move the Instituto de Botánica Darwinion to a new building located in the San Isidro district, built especially to contain the institute and also his retirement home. After 87 years of existence and five building extensions, the historic building of the Instituto de Botánica Darwinion of San Isidro maintains its integrity and attracts the attention of both the public and architecture and design professionals. Based on the study of building characteristics and the thought of Cristóbal M. Hicken, the main objective of this work is to evaluate whether the external and internal structure of the historic Darwinion building in San Isidro, together with the ornamentation and distribution of original functions of each room, respond only to an aesthetic and functional design or if, in addition, they have a symbolic meaning, a vision of the world, a silent message for those who want (and know how) to understand. With this central purpose as a guide, we carried out a multidisciplinary investigation to reconstruct Cristóbal M. Hicken’s vision in the design of the Instituto de Botánica Darwinion of San Isidro. We started from the analysis of the original building in the San Martín district in search of any possible design background, to then focus the attention entirely on the building in San Isidro. Plans, public documents, correspondence, historical photographs, academic and dissemination articles of the time, pre-Hispanic South American ethnographic information, Argentine historical information between 1860 and 1930, and interviews with relatives and historians were studied. In short, the Instituto de Botánica Darwinion in San Isidro was created as a museum and a laboratory plus a home. The design of the museum agrees with the concept of “temple of Botany” manifested by Cristóbal M. Hicken himself, and whose first sign is observed in the etymology of the name of the institute. Its ornamentation is eclectic, since it combines symbols of Andean pre-Hispanic cultures with symbols of Western civilization, and it is structured according to each room (portal, front rooms, herbarium, library) and orientation (towards the street or towards the inner garden). This ornamentation works like a discourse in symbolic key with multiple messages for the visitor: it reflects an original, foundational, and ancient Argentine identity, which in turn communicates that the Darwinion is a place where a silent and fertile unveiling of the knowledge, of the secrets of evolution, takes place protected from evils and misfortunes by Nature itself. The design plan of the institute, the portal, the access terrace, and the internal garden convey desirable masonic values through the symbolic language, typical and traditional of Freemasonry. Likewise, we show evidence of Dr. Cristóbal M. Hicken’s great interest in Andean pre-Hispanic cultures, of his refined knowledge of Greco-Roman mythology, his belonging to Argentine Freemasonry and consequent ability to symbolic language, and his knowledge of construction, cosmology, and analytic geometry. For these reasons, and considering his participation in the supervision of the building work declared by the newspapers of his time, the probable direct intervention of Cristóbal M. Hicken is proposed both in the design of the building of the Instituto de Botánica Darwinion of San Isidro, as well as in the design of its ornamentation. In addition, evidence is provided of the possible intervention of Arturo Prins and Fernando de Estrada in the project of the building.