Although in these later instances Iset is referred to as Great Royal Wife, during the reign of Thutmose II the great royal wife was Hatshepsut. The great royal wife served in many official roles, including being the high priestess in the temple. Thutmose II died in 1479 BC and, after his death, Hatshepsut was named as the next pharaoh and Thutmose III as co-regent. Thutmose III became the head of the armies of Hatshepsut.
Hatshepsut ruled as pharaoh until her death in 1458 BC when her co-regent, Thutmose III, became pharaoh. At that time Iset received the title of "King's Mother" (since her son had become pharaoh) and she may then have been designated as a royal wife if she had not been previously when he was the co-regent. At the time Thutmose III became pharaoh, his royal wife is thought to have become, Neferure, the daughter of Hatshepsut and Thutmose II, who had served in this role throughout the reign of her mother as pharaoh. Neither Neferure nor their issue survived the death of Thutmose III, and a minor wife, Hatshepsut-Meryetre, became the mother of his successor.
There is no time when Iset would have been designated as the great royal wife during her lifetime, but there were efforts toward the end of the reign of Thutmose III when he designated his son as co-regent for two years, and to a much greater amount during the reign of his son as Amenhotep II, to rewrite history. Amenhotep II altered records and took credit for things Hatshepsut accomplished. Rewriting the history of his father, Thutmose III, in efforts to eliminate Hatshepsut would have necessitated elevating his father's mother to the level of Hatshepsut's mother, hence the misrepresentation of Iset as the great royal wife of Thutmose II. The erasures and rewritings were not complete, however, and the accurate history was not lost.
It is not certain whether Iset was a concubine or a secondary wife of Thutmose II, but she would have been from the royal lineage of Egyptian women to be either—because the royal line was carried by the women. She also received the title "God's Wife", but probably only retroactively, after her death. Thutmose II would have been deified after his death, following the traditions of his time, so that would be the reason she was granted that title later.