The famous fresco “ The Creation of Adam ” (c. 1511), painted by the Renaissance master Michelangelo Buonarroti (1475–1564) on the ceiling of the Sistine Chapel in Rome, Italy, is one of the most emblematic works of Western art. The fresco depicts the biblical creation of Adam, the first human being, at the moment he receives life from God. Over the centuries, this work has become a symbol of the integration of the visual arts, the humanities, and medical sciences, inspiring numerous scholarly interpretations. Despite the extensive literature on this fresco, some anatomically depicted features with potential semiological significance remain insufficiently explained. However, an iconodiagnostic approach may offer further insight into the possible rationale for their representation. Accordingly, the present description provides novel evidence supporting the interpretation that Michelangelo’s Adam exhibits semiological signs suggestive of a hemodynamic disorder known as superior vena cava syndrome. Careful observation of the fresco indicates that Michelangelo’s representation of Adam appears to exhibit two semiological signs: enlargement of the region of the thyroid gland ( goiter ) and external jugular vein distention. Considered together and interpreted with due caution, these features, in association with the iconographic context of Adam, provide the main semiological basis for this iconodiagnostic hypothesis. These observations illustrate how iconodiagnostic analyses can contribute to the medical humanities by encouraging semiological reasoning through the study of Renaissance masterpieces. Furthermore, such interdisciplinary approaches highlight the educational potential of art in medicine, emphasizing the value of artworks in contemporary medical education and the development of visual literacy.