In 1880, the director of the Uffizi Gallery asked Leighton to contribute a work to the Gallery's famous collection of artist's self portraits. The lack of works by contemporary British artists was keenly felt, and Leighton was asked to suggest the names of others who might be approached. His portrait was submitted alongside those by Millais and Watts: the three form a striking contrast.
Leighton was conscious of his descent from Reynolds as President of the Royal Academy. In a famous self-portrait in the Royal Academy, Reynolds had depicted himself in doctor's robes, beside a bust of Michelangelo. Leighton likewise decided to present himself in the red robes of a doctor of Oxford University, with the medal of the President of the Royal Academy hanging down, but in a declaration of his artistic affiliation used the frieze of the Elgin Marbles as a backdrop. (A copy of the frieze embellished the artist's remarkable studio house that he had recently built in Holland Park). The picture is highly formal and stylized, and forms a marked contrast to Millais's portrait of himself in a casual coat, painting beside a mirror as he worked.
Leighton's portrait was exhibited at the Royal Academy in 1881, no. 119. A professional copyist was employed in Florence to make copies. This one descended in the family of Leighton's cousins at Loton Park in Shropshire. Another hangs in the town hall of Scarborough, where Leighton had been born in 1830. A further copy, by Sir Charles Holroyd, belongs to the Society of Dilletanti.