Macedonian king of Egypt, whose quasi-legitimate royal status compelled him to depend heavily upon Rome for support for his throne. During his reign Egypt became virtually a client kingdom of the Roman Republic. He was the first Ptolemy to include Theos (God) in his formal title. (Auletes was not part of his formal title.)

Following the sudden, violent deaths of the last two fully legitimate members of the Ptolemaic family in Egypt, the people of Alexandria in 80 invited Ptolemy XII to assume the throne. Although he was known as a son of Ptolemy IX Soter II, his mother was a mistress of Soter, not a wife. In 103 he was sent by his grandmother, Cleopatra III, queen of Egypt, in the company of his brother and Ptolemy XI Alexander II, his predecessor, to Cos, an Aegean island near Asia Minor, for safekeeping. Captured in 88 by Mithradates VI Eupator, ruler of Pontus, a kingdom in Asia Minor that was then at war with Rome, young Ptolemy appeared in 80 in Syria, from where, according to Cicero, he arrived in Egypt, while his brother became king of Cyprus.

Shortly after his arrival in Egypt, Ptolemy married Cleopatra V Tryphaeana (“the Opulent”), his sister, and in 76 he was crowned in Alexandria according to Egyptian rites. At Rome, however, anti-Senate politicians in 65 raised the issue of Ptolemy's legitimacy, producing a questionable will of Ptolemy XI Alexander II purporting to bequeath Egypt to the Roman people. Ptolemy, seeking Roman support, sent troops to assist the consul and general Pompey the Great in Palestine. Cicero, representing Pompey's interests, persuaded the Senate to oppose Roman annexation. Facing serious opposition from the people of Alexandria and still unsure of his status at Rome, Ptolemy bribed Julius Caesar, one of the Roman consuls for the year 59, with 6,000 talents, in return for which Caesar passed a law acknowledging his kingship. Rome nevertheless divested Egypt of Cyprus the next year, and, when his brother in Egypt failed to support him, the island's king committed suicide.

The loss of Cyprus and Ptolemy's submissive attitude to Rome outraged the people of Alexandria, who drove Ptolemy out of Egypt and accepted his queen, Tryphaeana, and his eldest daughter, Berenice IV, as rulers in 58. Residing at Pompey's villa at Rome, he employed bribery to obtain the support of the Roman senators. He also arranged the assassination of delegations sent by his opponents from Alexandria, where, following his queen's death, the people had made Berenice IV sole ruler. While the Senate delayed an answer, Ptolemy, continuing to dispense bribes, fell deeper into debt to Roman moneylenders. Late in 57 the Senate passed a resolution to support Ptolemy, but, when a prophecy forbade the granting of active aid, the Egyptian king departed for Ephesus, a city in Asia Minor.

In 55, after promising Pompey's lieutenant Aulus Gabinius, proconsul of Syria, 10,000 talents, Ptolemy was returned to Egypt with a Roman army. Once restored, he executed his daughter, who had headed the opposition at Alexandria. Shortly before his death in 51 he proclaimed his eldest surviving daughter, the celebrated Cleopatra VII (Cleopatra), and his eldest son coregents. His extensive bribery left Egypt in financial trouble.