HMN 2026: What is the new explanation for the mystery death of Botticelli’s Birth of Venus model, Simonetta Vespucci

A paper on new research into the cause of death of Simonetta Vespucci, model for the world-renowned Birth of Venus by Sandro Botticelli, has been published by researchers at Queen Mary University of London, Universita Campus Bio-Medico di Roma and the University of California in the journal Endocrinology, Diabetes & Metabolism.

In 2019, the researchers suggested she probably suffered from a pituitary adenoma. In this new paper, they looked at more documents and concluded that an expansion of the adenoma causing tumor apoplexy—a sudden medical emergency—was the probable cause of her premature death at age 23.

Simonetta Vespucci, born Cattaneo (Liguria, Jan. 28, 1453), was well known in Florentine high society for her manners and intellect, and was given the title La Sans Par (“the Unrivalled”) by the humanist Poliziano. She was close to both Lorenzo and Giuliano de’ Medici.

In 1469, she married Marco Vespucci, a descendant of a noble family of Florentine bankers. She was painted by her devoted admirer and close friend Sandro Botticelli five times. When she died, her body was exposed to public veneration, vestita e scoperta (dressed in white, face uncovered), the highest homage to illustrious Renaissance figures. She still rests in the church of Ognissanti, and in 1510 Sandro Botticelli asked to be buried at her feet, in a final devotional act to his muse.

Symptoms behind her death

While Simonetta’s features are now thought to embody the aesthetic canons of the Renaissance, the authors researched her premature death, particularly the symptoms of her final days, and concluded that both her symptoms and features suggest a pituitary tumor was the cause rather than the TB (consumption) once suspected. They also hypothesize that dancing or a suspected rape by the infamous Alfonso II D’Aragona, Duke of Calabria, could have precipitated a medical emergency.

“Letters between Piero Vespucci and Lorenzo de’ Medici about Simonetta’s final days discuss how she collapsed during a ball and was then resting in a darkened room where she suffered from terrible headaches, hallucinations, vomiting and high fever. These are all symptoms of a rapidly expanding pituitary tumor,” said first author Dr. Domiziana Nardelli, Ear Nose and Throat (ENT) resident at the Universita Campus Bio-Medico di Roma.

“Botticelli’s Allegorical portrait of a Woman shows a woman—the model is Simonetta Vespucci—lactating, and yet we know she had no children. This is a surprising way to portray her, and we believe that this—along with changes in facial traits—could show the real physical symptoms of a prolactin-growth hormone secreting adenoma. We’ve confirmed this possible diagnosis using a facial recognition algorithm based on a pre-trained deep learning model on five portraits of Simonetta.

“It’s also possible that the irregular eye positioning in the Birth of Venus—the ‘strabismus’ or squint later considered a trait of piety and beauty—may be caused by the pituitary tumor,” said senior author Paolo Pozzilli, clinical research professor at Queen Mary University of London.

Pozzilli’s next paper expands on this work on the squint or misalignment of her eyes.

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