See also Seal of the Prophets.

This is understood to refer to an unusually large mole on Muhammad's back. This birthmark is given as the physical proof that Muhammad is a true prophet.

The meaning is apparent from the hadiths given below.

Narrated As-Sa'ib:
My aunt took me to Allah's Apostle and said, "O Allah's Apostle! My nephew is ill." The Prophet touched my head with his hand and invoked Allah to bless me. He then performed ablution and I drank of the remaining water of his ablution and then stood behind his back and saw "Khatam An-Nubuwwa" (The Seal of Prophethood) between his shoulders like a button of a tent. (Sahih Bukhari 7.574. see also Sahih Bukhari 4.741)
Another hadith explains that this is a large mole:
Narrated As-Sa'ib bin Yazid:
My aunt took me to the Prophet and said, "O Allah's Apostle! This son of my sister has got a disease in his legs." So he passed his hands on my head and prayed for Allah's blessings for me; then he performed ablution and I drank from the remaining water. I stood behind him and saw the seal of Prophethood between his shoulders, and it was like the "Zir-al-Hijla" (means the button of a small tent, but some said 'egg of a partridge.' etc.) (Sahih Bukhari 1.189. see also Sahih Muslim 4.5793)
This mole, as claimed by Muslims, is the physical proof that Muhammad is indeed the fulfilment of the biblical passage in Isaiah 9:6:
"Unto us a child is born, and unto us a son is given, whose government is on his shoulder."
Ali Tabari, for example, says that the verse says in Hebrew that
"The sign of prophecy is on his shoulder." (Ali Tabari, The Religion and the Empire, trans. Mingana, pp. 95)
Lately, M.I. Liaqath Ali ([1]) says that in John 6:27, "Jesus wanted his posterity to look for the Prophet (Pbuh) possessing this singular physical seal and not the usual miscellaneous non-physical signs, however noticeable." [emphasis his. He seems to suggest that the physical sign is the most important, and that all other spiritual attributes are not important. We wonder why he didn't quote the verse in full, when he quoted verses surrounding it]. A simple reading of the full verse, however, shows that John 6:26-27 says that
Jesus answered, "I tell you the truth, you are looking for me, not because you saw miraculous signs but because you ate the loaves and had your fill. Do not work for food that spoils, but for food that endures to eternal life, which the Son of Man will give you. On him God the Father has placed his seal of approval." (John 6:26-27)
The pasage clearly shows that this "seal of approval" is on "him", which is clearly the "Son of Man", a title Jesus used for Himself. Muhammad did not have this title. It is just ludicrous for Jesus to, all of a sudden, use the title to refer to Muhammad. There simply is no space to squeeze Muhammad into that verse.

Further reading: Muhammad and the Seal of Prophethood

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