The authors agree that this surname derives from the biblical name of the prophet Isaiah, known in Hebrew as Isaiah or Isaijah. He is the first of the four Major Prophets, whose cult in the Christian tradition is linked to 6 July.

E. Rossoni notes that the forms of the surname —Isaia, Isaja, Isaija, Isajia and related variants— derive directly from the biblical name, in some cases through processes of aphaeresis, and would probably indicate a Sephardic Jewish origin. Isaia has two areas of concentration: one in the Catania area and another in the Cuneo area. Isaja is considerably rarer. The forms Isaija and Isajia are less frequent still and appear proper to eastern Sicily. Saija is recorded specifically in the Messina area. Sajia is practically unique and is probably attributable to transcription errors for Saija.

A. Bongioanni stresses that the Hebrew name has a meaning analogous to that of Giosuè and Gesù, and is especially venerated in the Church because, according to Saint Jerome, the prophet seemed not so much a prophet as an evangelist. Bongioanni further points to a possible connection with the surname Saglietti, called in Piedmontese Sajét.