The altarpiece was made during Parmigianino’s stay in Bologna in the years from 1527 to 1530. Having fled from Rome, which had been invaded and plundered by the landsknechts of Emperor Charles V, in the Emilian city, the artist spread the new ideal of beauty that he had helped define in Rome with Pope Clement VII’s Last Supper together with Perin del Vaga, Giulio Romano and Rosso Fiorentino. 

The fulcrum of the composition of Santa Margherita is the mystical marriage between Baby Jesus and the Saint sealed by an intense look of love.

The Virgin turns towards San Petronius, absorbed, like St. Jerome, in contemplating the event, while the Angel, with an unpredictably ambiguous glance, calls the viewer's attention.

In the lower-right margin a dragon with open jaws is depicted, a clear reference to the iconography of the Saint.

In the subversion of every classical rule in terms of space and form, Parmigianino brings together the figures in the intimacy of a contained and asymmetric space, in a composition that uses an innovative language that was to become a school for the entire next generation. Thanks to a highly fluid pictorial approach, the virtuosity of a very personal style emerges, oriented, on the one hand, toward creating optical sensations, and on the other, toward seeking sophisticated elegance such as the elaborate hairstyles in the two female figures.

No longer subjected to the limits of imitating reality, the figures emerge from the canons of traditional sacred representation and are articulated in sinuous movements and elongated forms, while the setting in a shady wood, perhaps nocturnal, becomes a metaphor for an apprehension that reflects the complexity of the time.