Recorded in a wide range of spellings including Santo, Santelli, Santella, Santaro, Santarella, Santarello, Sentinella and Sentinelli, this is a surname of Italian origins. Derived from the Roman (Latin) word 'sanctus' it is either occupational and originally described a maker of saintly images and possibly of heraldic blazons, flags, and banners, or it was a nickname for a saintly person, Santo being a popular first name in Southern Italy. To the base name has been added over the centuries a wide range of diminutive, double diminutive, or patronymic suffix denoting the son of Santo, or Little Santo, or the kin of Santo, or the son of the son of Santo. Italian surnames are traditionally the most difficult of all European surnames to research. Although hereditary in that the base name was usually (but not always) unchanged in spelling, the suffix was changed at will, and with many families only became "fixed" in spelling as late as the 20th century. Furthermore Italy did not become a nation-state until after 1860, centralised records as such rarely existing until after that date. Examples of the surname recordings taken from surviving church registers include: Francisco Santarella, at San Severo, Foggia, on June 11th 1854, Ercole Santarello, the son of Petro and Elizabetta Santarello, at Venezia, on August 30th 1905, and Acieto Sentinelli, whose daughter Clara was christened at Atessa, Chieti, on October 23rd, also 1905.

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