"Among the most noble houses, which may properly be called palaces, is that of Count Grignano, located in the large square of the Carmine, occupying with its façade an entire wing of said square, distinguished within by a private garden."

Thus wrote the Marquis of Villabianca at the end of the 18th century in his History of Marsala.

Palazzo Grignano (or Grignani—the spelling has varied over the centuries) stands in the historic and picturesque Piazza Carmine, which is adorned by the ancient convent of the Carmelite friars, with its annexed church dedicated to the Madonna Annunziata and its octagonal bell tower, as well as by the neoclassical Palazzo Vaccara, now converted into a hotel.

Next to Palazzo Grignano once stood the Palazzo of the Cappasanta family, who were prominent figures in the city's life until the 16th century. Subsequently, as the Cappasanta family either died out or moved away, their palace passed to the Grignano family, who expanded their residence southward. However, they never unified the façades of the two buildings, leaving the frontage appearing unfinished.
It is likely that financial difficulties faced by the family prevented the harmonization of the two structures.
Palazzo Grignani is a massive 18th-century building that nonetheless retains some features from earlier centuries, such as three architraved windows framed by a horizontal cornice in the Mannerist style.
The large round-arched portal is framed by two tall smooth-rusticated pilasters supporting a horizontal cornice.
Of the balconies on the second floor, only one—with its dynamic and harmonious design—features a wavy threshold supported by volute brackets and a wrought iron railing shaped like a goose breast.
The shaped jambs support a broken pediment in which a medallion rich in decorative elements is set.
A deeply projecting cornice supported by brackets crowns the building.

On the side façade along Via Garraffa, the only notable element is a small balcony with the characteristic 18th-century goose-breast railing.

In the rivelo (tax declaration) of Count Antonio XI Grignano, there is a detailed description of the palace that proves useful for understanding the building’s original structure, now significantly degraded by frequent alterations over the last century and decades of neglect.

The Count “states he owns a large house for his own residence, consisting of three floors; and beginning with the ground level, he says there are in the courtyard five arches supported by four white marble columns and nine doors.” A detailed description follows of the ground-floor rooms, where there were a stable, two large storerooms with three arches that held two hundred salme (a local unit of measure) of wheat, the carriage room, two houses for the servants, another room that could hold one hundred salme of wheat, a coal room, another room capable of holding 80 salme of wheat, and a storeroom for storing straw.
A door led “to a private garden for recreation, consisting of two tumoli (units of land) with four vine-covered paths,” containing fig trees, apple trees, pear trees, pomegranates, peach trees, and various other plants. In this garden, enclosed by a stone wall, there was running water, a well whose water was drawn using a senia (a type of water wheel), and a small house for the gardener.
A white marble staircase led to the first floor, where the bedrooms and the kitchen were located, the latter being supplied with running water through a trigger-type spout. The second floor was accessed by the same marble staircase, which opened into a gallery with three arches supported by three inlaid stone pillars; in this gallery there was a door leading to the main hall, which in turn opened onto two doors giving access to additional bedrooms, a private chapel, and a covered terrace with glass windows.
The Count also owned some small houses adjacent to the palace, located in three courtyards along what is now Via Garraffa.