The complete phrase is "it makes not one iota of difference," and believe it or not, it is tied to the Arian heresy. One of the problems Arius had with what became conventional Christianity was the nature of Jesus vs. God the Father. Arius and his followers believed that Jesus had a separate existence and was subordinate to the Father. During the Council of Nicaea, Arius argued with others over the word homoousios (Greek 'homo'=same + 'ousios'=substance). This is the word that was translated into the Latin consubstantialem in the Nicene Creed, translated into English as "one in being." Arius argued for heteroousios ('hetero'=other).
|The Trinity Shield; Arian or not?|
Or did it? There really is no evidence for that origin, although it sounds good, and sufficiently obscure and scholarly that no one wants to argue with it.
Some try to tie this into Matthew, 5:18:
For truly, I say to you, until heaven and earth pass away, not an iota, not a dot, will pass from the Law until all is accomplished. [English Standard Version]
For truly I tell you, until heaven and earth pass away, not one letter, not one stroke of a letter, will pass from the law until all is accomplished. [New Revised Standard Version]The argument for this origin (I guess) is that an iota is the smallest imaginable amount of difference, or the smallest written bit of the law, and even that will/must not alter before the end comes.
There may be a simpler reason for the saying, however, that goes back to the Greek language itself. The letter iota could be the second part of a diphthong, and the first vowel could be long or short. If the first vowel were long, the iota lost strength and ceased to be pronounced, but in written Greek it was still added as a subscript below the preceding long vowel. So αι (alpha + iota) became ᾳ, ηι (eta + iota) became ῃ. The iota, in some circumstances, became the least important letter, reduced in size as well as in the way it affected pronunciation. To me, this is a potential (and potent) origin story for an "iota of difference" being completely insignificant.
*By the way, Semi-Arianism is alive and well in 21st century America, apparently.