Born at Sampierdarena (in what is modern Genoa), he was the son of Franceschetto Cybo and Maddalena de' Medici, daughter of Lorenzo de' Medici. His uncle was Pope Leo X. His paternal grandfather was Pope Innocent VIII. In 1520 the former, in agreement with Lorenzo's elder brother, Cardinal Innocenzo Cybo, arranged his marriage to Ricciarda Malaspina, heir of the Malaspina family, with whom he founded the new house of Cybo-Malaspina:^[1] it was to hold the Marquisate (then Duchy) of Massa and Carrara until 1829, when it was annexed to the Duchy of Modena and Reggio, ruled by a successor of theirs in the female line.

The marriage turned out to be decidedly stormy. Lorenzo was co-owner ("co-padrone") of his wive's marquisate of Massa and Carrara from 1530 until 1541, when she succeeded in having him removed by decree of Emperor Charles V.^[2]

Their son Giulio, after managing with his father's help to forcibly dispossess Ricciarda from 1546 to 1547, ended up beheaded for treason in Milan in 1548.^[2]

Lorenzo Cybo died the following year, in 1549, and was succeeded as Duke of Ferentillo by his younger son Alberico, although perhaps born from his mother's adulterous relationship with Lorenzo's brother, Cardinal Innocenzo Cybo.^[2]

In 1553, upon his mother's death, Alberico succeeded her too, adding, by testamentary disposition, the style Malaspina to his paternal surname.^[2]

A skilled soldier, he held the position of commander-in-chief of the Papal Army.

• Portrait of Lorenzo Cybo

• Calonaci, Stefano (2006). "MALASPINA, Ricciarda". Dizionario Biografico degli Italiani (in Italian). Vol. 67. Rome: Istituto dell'Enciclopedia Italiana. Retrieved 12 September 2023.
• Petrucci, Franca (1981). "CIBO, Lorenzo". Dizionario Biografico degli Italiani (in Italian). Vol. 25. Rome: Istituto dell'Enciclopedia Italiana. Retrieved 12 September 2023.