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Saluzzo (Salusse in Piemontese, Saluces in French) was a civitas (tribal city state) of the Vagienni, or mountain Ligures, and later of the Salluvii. This district was brought under Roman control by the Consul Marcus Fulvius circa 125BC.

In the Carolingian age it became the residence of a count; later, having passed to the Marquesses of Susa, Manfred I, son of Marquess Bonifacio del Vasto, on the division of that principality became Marquess of Saluzzo; this family held the marquisate of Saluzzo from 1142 to 1548. The marquisate embraced the territory lying between the Alps, the Po and the Stura, and was extended on several occasions. In the Middle Ages it had a chequered existence, often being in conflict with powerful neighbours, chiefly the Counts (later Dukes) of Savoy. After Manfred II's death, his widow had to accept a series of tributes, which were to be later the base of the House of Savoy's claims over the increasingly feebler marquises' territories. Thomas III, a vassal of France, wrote the romance Le chevalier errant ('the knight-errant').

Ludovico I (1416–75) started the Golden Age of the city and imposed himself as a mediator between the neighbouring powers. Ludovico II constructed a tunnel, no longer in use, through the Monviso, a remarkable work for the time. With the help of the French he resisted a vigorous siege by the Duke of Savoy in 1486, but in 1487 yielded and retired to France where he wrote L'art de la chevalerie sous Vegèce ("The art of chivalry under Vegetius", 1488), a treatise on good government, and other works on military affairs. He was a patron of clerics and authors. In 1490 Ludovico regained power, but after his deaths his sons struggled longly for the rule and impoverished the state.

After long struggles for independence, the marquisate was occupied (1548) by the French, as a fief of the Crown of France - with the name of Saluces - and remained part of that kingdom until it was ceded to Savoy in 1601. In 1588 Charles Emmanuel I of Savoy took possession of the city. Thenceforward Saluzzo shared the destinies of Piedmont, with which it formed "one of the keys of the house" of Italy.

The Marquisate of Saluzzo is the setting of Boccaccio's tale of Griselda, the final story in the Decameron, as well as Chaucer'sClerk's Tale in The Canterbury Tales