Her father was a member of the Genoese minor nobility and encouraged his five daughters to develop artistic skills alongside their humanist education.

Contemporary critics considered her skill exemplary; according to seventeenth-century biographer Filippo Baldinucci, Lucia had the potential to "become a better artist than even Sofonisba" had she not died so young.

[2] One of her extant paintings, Portrait of Pietro Manna, (early 1560s)[3] was praised by Giorgio Vasari, who saw it when he visited the family after her death.

The man sitting in the portrait is thought to be a relative to the Anguissola family, and commonly assumed to be a physician or doctor, but that is false.

Lucia's skill is demonstrated in her ability to illustrate the sitter's personality in the animated face with a cocked eyebrow and the shoulders held at different levels.

One art historian has suggested that Lucia Anguissola's "suspended" and "gloomy" gaze alludes to her feelings about living in Sofonisba's shadow.

Two portraits, in the Pinacoteca Tosio Martinengo in Brescia and the Museo Poldi Pezzoli in Milan, probably of Minerva Anguissola, may also be by Lucia.