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As a proto-Christian saint

Seneca's writings were well known in the later Roman period, and Quintilian, writing thirty years after Seneca's death, remarked on the popularity of his works amongst the youth. While he found much to admire, Quintillian criticized Seneca for what he regarded as a degenerate literary style—a criticism echoed by Aulus Gellius in the middle of the 2nd century.

The early Christian Church was very favourably disposed towards Seneca and his writings, and the church leader Tertullian possessively referred to him as "our Seneca". By the 4th century an apocryphal correspondence with Paul the Apostle had been created linking Seneca into the Christian tradition. The letters are mentioned by Jerome who also included Seneca among a list of Christian writers, and Seneca is similarly mentioned by Augustine. In the 6th century Martin of Braga synthesized Seneca's thought into a couple of treatises that became popular in their own right. Otherwise, Seneca was mainly known through a large number of quotes and extracts in the florilegia, which were popular throughout the medieval period. When his writings were read in the later Middle Ages, it was mostly his Letters to Lucilius —the longer essays and plays being relatively unknown.

Medieval writers and works continued to link him to Christianity because of his alleged association with Paul. The Golden Legend, a 13th-century hagiographical account of famous saints that was widely read, included an account of Seneca's death scene, and erroneously presented Nero as a witness to Seneca's suicide. Dante placed Seneca (alongside Cicero) among the "great spirits" in the First Circle of Hell, or Limbo. Boccaccio, who in 1370 came across the works of Tacitus whilst browsing the library at Montecassino, wrote an account of Seneca's suicide hinting that it was a kind of disguised baptism, or a de facto baptism in spirit. Some, such as Albertino Mussato and Giovanni Colonna, went even further and concluded that Seneca must have been a Christian convert.