E. De Felice notes that the surname has as its base the feminine name Regina, from the Latin regina ("queen"), used in Christian Latinity as an attribute of the Virgin Mary (Regina coeli) and as an auspicious name for the newborn girl. He indicates that it is diffused sporadically throughout Italy, is more common in Sicily as Reina or Riina, and appears in Friuli in dialect forms.

A. Bongioanni suggests that there are two equally valid etymologies: the Latin one ("queen") and the Germanic one, derived from Regino and Reginald, names in which the first element ragin- means "counsel, decision." He mentions that three female saints bear this name, one of the 3rd century (7 September).

E. Rossoni agrees on the Latin origin and specifies that the surname derives, directly or in a dialect form, from the Late Latin name Regina, referring to the Virgin Mary (regina coeli, "queen of heaven").

Rossoni distinguishes the distribution of the different forms: Regina is typical of southern Italy; Regini is more proper to the centre; Reina seems native of western Sicily, although there are Lombard areas; Reini is almost non-existent.