The authors differ on the etymology of this surname. E. De Stefani offers the best-documented analysis: the surname is native to Preone, in Carnia —the mountainous area of northern Friuli, in the province of Udine—, and is attested from the 16th century in forms such as Dilinisa or de nilisa; the present-day form appears in the 18th century. De Stefani rules out both the connection with the feminine name Elena or Maddalena and the hypothesis of an origin in the Slovene surname Lenac (from the Slovene len, "lazy") with the suffix -isa, considering them incompatible with the available attestations.

According to De Stefani, the soundest etymology starts from the crossing of two old Friulian feminine names: Ignilissa —a variant of Ignilussa, a hypocoristic of Agnule, the equivalent of "Angela"— and Linissa —a variant of Linussa, a frequent name in medieval Friuli. Through metathesis and deglutination of the preposition de, the form Linisa would have been reached first, and then, by vowel differentiation, Lenisa. The documentary sources do not allow one to decide with certainty which of the two bases is the original. The surname is also recorded in Udine, in Fratta —a hamlet of Caneva, in the province of Pordenone— and in the Treviso area, in Pieve di Soligo and Cordignano.

For his part, F. De Laurentiis holds that the surname derives from the name Lena, a hypocoristic by aphaeresis of Maddalena. This name comes from the Latin Magdalena and its Greek parallel Magdalene, both linked to the New Testament tradition, where the name goes back to the Palestinian locality of Magdala —in Hebrew Migdal, "tower".