However, there is evidence which implies that cult of Serapis existed before the Ptolemies came to power in Alexandria – a temple of Sarapis (or Roman Serapis) in Egypt is mentioned in 323 BC by both Plutarch (Life of Alexander, 76) and Arrian (Anabasis, VII, 26, 2). The common assertion that Ptolemy "created" the deity is derived from sources which describe him erecting a statue of Sarapis in Alexandria: this statue enriched the texture of the Sarapis conception by portraying him in both Egyptian and Greek style. Though Ptolemy I may have created the cult of Sarapis and endorsed him as a patron of the Ptolemaic dynasty and Alexandria, Sarapis was a syncretistic deity derived from the worship of the Egyptian Osiris and Apis (Osiris + Apis = Oserapis/Sarapis; Coptic: ⲟⲩⲥⲉⲣϩⲁⲡⲓ) and also gained attributes from other deities, such as chthonic powers linked to the Greek Hades and Demeter, and benevolence linked to Dionysus.
Serapis continued to increase in popularity during the Roman period, often replacing Osiris as the consort of Isis in temples outside Egypt. In 389, a Christian mob led by the Patriarch Theophilus of Alexandria destroyed the Alexandrian serapeum, but the cult survived until all forms of pagan religion were suppressed under Theodosius I in 391.
"Serapis" is the most common form used in Latin, but epigraphical sources also show the occasional use of "Sarapis". Both Σάραπις, Sárapis and Σέραπις, Sérapis appear in Greek, as well as Σαραπo Sarapo in Bactrian.
His most renowned temple was the Serapeum of Alexandria. Under Ptolemy Soter, efforts were made to integrate Egyptian religion with that of their Hellenic rulers. Ptolemy's policy was to find a deity that should win the reverence alike of both groups, despite the curses of the Egyptian priests against the gods of the previous foreign rulers (e.g. Set, who was lauded by the Hyksos). Alexander the Great had attempted to use Amun for this purpose, but he was more prominent in Upper Egypt, and not as popular with those in Lower Egypt, where the Greeks had stronger influence. The Greeks had little respect for animal-headed figures, and so a Greek-style anthropomorphic statue was chosen as the idol, and proclaimed as the equivalent of the highly popular Apis. It was named Aser-hapi (i.e. Osiris-Apis), which became Serapis, and was said to be Osiris in full, rather than just his Ka (life force).
The earliest mention of a Serapis occurs in the disputed death scene of Alexander (323 BC). Here, Serapis has a temple at Babylon, and is of such importance that he alone is named as being consulted on behalf of the dying king. The presence of Serapis in Babylon would radically alter perceptions of the mythologies of this era: the unconnected Babylonian god Ea (Enki) was titled Serapsi, meaning "king of the deep", and it is possible this Serapis is the one referred to in the diaries. The significance of this Serapsi in the Hellenic psyche, due to its involvement in Alexander's death, may have also contributed to the choice of Osiris-Apis as the chief Ptolemaic god.