It is the second of only four surviving portraits of women painted by Leonardo, the others being Ginevra de' Benci, La Belle Ferronnière and the Mona Lisa.

[11] The animal in her arms twists in a similar manner, resulting in considerable contrapposto with the lady,[12] a technique Leonardo explored earlier with the angel in the Virgin of the Rocks.

[1] The Lady with an Ermine is also connected to La Belle Ferronnière, as well as Leonardo's earlier Portrait of a Musician, due to the three paintings including black backgrounds.

[9] Though there are a few areas of minor damage, art historian Frank Zöllner insists the work is in "very good condition... similar to the equally well preserved Mona Lisa".

[20] Promotion of such an analysis largely began with the art historian Kenneth Clark,[20] who asserted in 1961 that the entire left side of the figure, as well as the background had been repainted.

[21] Scholars such as Adolfo Venturi, Angela Ottino della Chiesa and Jack Wasserman advanced the idea;[20] however, a 1992 technical analysis at the National Gallery of Art led by David Bull has confirmed that the damage was limited to the background.

[1][20] In light of this revision—with the primary damage being overpaint in the background—the art historian Martin Kemp noted that "the picture is in much better condition than the standard accounts suggest, and gives the clearest indication of the freshly brilliant quality of Leonardo's painting during his period at the Sforza court in Milan".

[12] She has a silk sbernia on over her left shoulder, though Leonardo has simplified the traditional manner of wearing—where it would be draped over both shoulders—potentially to avoid too much complication in the various elements of the painting.

Her hair is held in place by a fine gauze veil with a woven border of gold-wound threads, a black band, and a sheath over the plait.

The artist painted Cecilia's outstretched hand with a lot of detail, including the shape of each fingernail, the lines around her knuckles, and even the way the tendon in her bent finger moved as it bent[25] A recent study brings to the forefront and supports another so far little-followed hypothesis: the heroic character of Caterina Sforza, the lioness of Romagna, is proposed as being the model of this allegorical representation in which the mental strength and beauty that were attributed to Amazons in mythology.

The art historian Luke Syson notes that "Naturalism is not the point here; Leonardo has created a mythical beast, the composite of several animals he drew at this time".

[32] In his old age, Leonardo compiled a bestiary in which he recorded: "The ermine out of moderation never eats but once a day, and it would rather let itself be captured by hunters than take refuge in a dirty lair, in order not to stain its purity.

"[34] A drawing by Leonardo in pen and ink of c. 1490, housed at the Fitzwilliam Museum in Cambridge, depicts an ermine representing these ideals by surrendering to a hunter.

[37] Petrarch's poem, which describes Chasity as triumphing over Love, was often depicted in lavishly decorated chests (called cassone) which formed an important part of the wedding trousseau of brides from prominent backgrounds.

[44] She was married at approximately age six to a young nobleman of the house of Visconti, but sued to annul the marriage in 1487 for undisclosed reasons and the request was granted.

[46] It has always been known that Leonardo painted a portrait of Ludovico Sforza's mistress,[41] Cecilia Gallerani, but the Lady with an Ermine remained largely unknown to scholars until nearly the 20th century.

During the November Uprising in 1830, the 84-year-old Princess Czartoryska rescued it in advance of the invading Russian army, hid it, and sent it 150 km south to the Czartoryski palace at Sieniawa.

In 1940, Hans Frank, the Governor General of Poland, saw the painting there and requested it be returned to Kraków, where it hung in his suite of offices in the Wawel Castle.

Throughout the mid–late 20th century the work traveled the world more extensively than any other Leonardo painting, being exhibited in Warsaw (1952), Moscow (1972), Washington, D.C. (1991/92), Malmö (1993/94), Rome/Milan (1998), Florence (1999).