The authors agree that this surname derives from the Greek kállistos, meaning "most beautiful" or "the most beautiful". It is the superlative of kalós, "beautiful", with the sense of "the most beautiful" or "the best".

A. Bongioanni notes that it was originally a given name, and that of the five saints who bore it, the most venerated is Saint Callixtus, pope and martyr in the year 222, whose feast is celebrated on 14 October. P. Durante agrees on the Greek origin and on its function as a proper name. V. Blunda, for his part, highlights its use in Sicily, where the term functioned as a name of positive connotation or a nickname applied to the ancestor, which over time became a surname by family line.