The authors agree that this surname derives from the Greek personal name Kosmâs. E. De Felice notes that the name passed into the Latin of the imperial period as Cosmas and gave rise to the variants Còsmo and Còsimo. Its diffusion in Italy is linked to the cult, of Eastern origin and tradition, of the saints Cosmas and Damian of Cyrrhus in Syria, martyrs under Diocletian and considered protectors of physicians for the miraculous cures attributed to them.

V. Blunda specifies that the Greek form Kosmâs derives in turn from kosmos, with the sense of "order, world", and that the name was preserved in the Byzantine hagiographic tradition before becoming fixed as a surname in eastern Sicily by the habitual route of Greek personal names.

De Felice adds that the geographical distribution varies according to the type: the forms Cosma and Cusma, together with derivatives such as Cosmelli and Cosmini, are concentrated in the coastal zones of the northeast of Italy, in the regions of Veneto, Friuli-Venezia Giulia and Trentino-Alto Adige, while the other forms are peculiar to southern Italy. The variant Cusimano, old and popular in Sicily, might not be a simple derivative of Cosma in -ano, but the fusion and contraction of the names of the two saints: Cosma e Damiano would have given Cosm-ano.