Nature Communications, 2026. DOI: 10.1038/s41467-026-72566-7.

How did Botticelli’s model really die?

One of 15th-century painter Sandro Botticelli’s most famous works is the Birth of Venus, depicting the naked goddess, newly birthed, standing in a giant scallop shell. The model for the painting (disputed by some historians) was allegedly Simonetta Vespucci (nee Cattaneo), a renowned beauty in Florentine high society whom Botticelli greatly admired. He painted her five times before her untimely death in her early 20s. Her open coffin was carried through the streets of Florence. The poet Poliziano dubbed her “the Unrivaled” (La Sans Par).

It was long believed that Simonetta had succumbed to tuberculosis, but in 2019, Paolo Pozzilli of Queen Mary University of London and several co-authors argued that she may have suffered from a pituitary tumor (adenoma) that gradually increased in size due to prolactin and growth hormone secretions, citing her appearance in several portraits as evidence. This could have caused a sudden tumor-related fatal apoplexy.

Pozzilli et al. have now expanded their analysis in a paper published in the journal Endocrinology, Diabetes & Metabolism. For instance, they examined letters between Simonetta’s father-in-law, Piero Vespucci, and Lorenzo de Medici, which described how Simonetta had collapsed during a ball a few days before her death. Her symptoms included headache, hallucinations, vomiting, and a high fever, all symptoms of a rapidly expanding pituitary tumor, per the authors. Pozzilli et al. also think the tumor would explain the irregular eye positioning in the Birth of Venus, suggesting the model had a squint or a misalignment of the eyes, which will be the subject of future research.

Endocrinology, Diabetes & Metabolism, 2026. DOI: 10.1002/edm2.70261.