The city known today as Perugia appears in history under the name Perusia as one of the twelve confederate cities of Etruria. It is mentioned for the first time in an account of the war between the Etruscans and the Romans of the years 310 and 309 BC; later it took part in a rebellion in the year 295 and was attacked and forced, together with Vulsinii and Arretium (Arezzo), to sue for peace the following year.

From this ancient Latin name, Perusia, and from its later Italian evolution, Perugia, arose numerous Italian surnames linked to a common geographic and ethnic origin. All of them reflect, in different ways, the medieval identification of a person according to their place of provenance, a very common practice in Italy between the Middle Ages and the Renaissance.

The surnames Perugini, Peruggini, Perugina, Perugino, Perugi, Peruselli, Perusi, Perusini and Perusino would derive mainly from dialectal and regional forms of the place name Perugia, originally indicating that the first bearers came from the comune of Perugia, in the region of Umbria. However, some variants could also derive from the Latinized medieval name Perusius or from hypocoristic forms such as Perusinus, used in ecclesiastical, notarial and academic documents drawn up in Latin. In the Middle Ages it was very common to Latinize names and demonyms; thus a person identified in Italian as "the Perugian" could appear in Latin registers as Perusius, that is, "originating from Perusia."

The linguistic evolution of these surnames followed different paths according to the Italian regions and local dialects. From the line derived directly from the place name Perugia arose forms such as Perugino and Perugini. The term Perugino was originally a singular demonym meaning "man of Perugia," while Perugini represented its plural or family form, the equivalent of "those of Perugia" or "descendants of Perugians."

• Perugini is currently very widespread in central Italy, especially in Romagna, Tuscany, the Marche, Umbria and Lazio, probably constituting the most diffused and standardized variant of this onomastic family.
• Perugino is recorded mainly in Campania, Calabria and Apulia, preserving an older form closer to the medieval demonym.
• Peruggini, with a double "g," constitutes a dialectal variant typical of Naples and the Neapolitan area, probably the product of regional phonetic adaptations proper to southern Italy.
• Perugina is an absolutely rare surname, documented in Campania, and seems to represent a feminine or dialectal variant of the same demonym origin.
• Perugi, on the other hand, appears scattered across different points of Italy and can be interpreted as a regional phonetic simplification derived from Perugia or Perugini.

In parallel there is another line of surnames linked to the ancient Latin name Perusia. From this root would derive the learned medieval form Perusius, used especially in documents written in Latin. Over time, Perusius evolved phonetically towards Perusi, following a process very frequent in the transition from Latin to Italian, in which many endings in -ius disappeared or were simplified. From Perusi arose new family and patronymic variants by means of Italian regional suffixes.

• Perusi is specific to the province of Verona, particularly to Negrar, Bussolengo and San Pietro in Cariano, and preserves a clearly more archaic and Latinizing sound than Perugini.
• Perusini, extremely rare, would seem to be of Friulian origin, especially associated with Sedegliano, in the province of Udine. The suffix -ini has a patronymic and family value, so Perusini can be interpreted as "the descendants of Perusi" or "the family of Perusi."
• Peruselli, absolutely rare, seems to originate from the Milan area and represents a Lombard evolution by means of the suffix -elli, very characteristic of northern Italy. Perusino, almost unique, would preserve a singular medieval structure derived possibly from Perusinus, a Latin hypocoristic or diminutive form related to Perusia.

The evolution of these variants allows one to observe how a single historical origin was transformed in different ways according to the Italian regional dialects. While Perugini and Perugino represent a line more directly linked to the vernacular Italian derived from Perugia, the forms Perusi, Perusini, Peruselli and Perusino preserve a more Latin and medieval stamp linked to the ancient name Perusia and to the learned form Perusius. Both lines coexisted for centuries and often mixed in historical documents, since scribes, priests and notaries alternated between Latin and the local vernaculars.

In this context it is also important to mention the Italian Jewish onomastic tradition. Among the Hebrew families of Italy it was frequent to adopt surnames derived from Italian cities and regions, especially between the Renaissance and the modern age, when many communities began to fix hereditary surnames. Cases such as Ancona, Modena, Modigliani, Pontecorvo or Tedeschi respond to this same phenomenon. For this reason, the surname Perugia and some of its variants may also appear in Italian Jewish families without possessing a particular meaning in Hebrew, but simply as toponymic surnames linked to the family’s place of residence or provenance.

Finally, it should be noted that not all phonetically similar surnames necessarily belong to this same etymological root. An interesting case is Peruzzi, which in some lines would derive from the affectionate diminutive of Piero or Pero, from which later arose patronymic variants such as Peruzzo, Peruzzi and finally Peruzzini. In this case, the surname would have a patronymic rather than toponymic origin, originally meaning "the descendants of Peruzzi" or "the sons of Piero." This shows how the phonetic similarity between Italian surnames does not always imply a common historical origin, since different linguistic lines may converge in very similar forms over the centuries.