[1][2] Scupoli travelled to Milan in 1578 to participate in a diocesan reform[1] and later began ministering, caring for patients of the Plague around 1581.

[2] For reasons that are still unclear, in 1581, Scupoli was accused of an "atrocious crime"[a] and removed from the priesthood sometime prior to 1585 and sentenced to one year in prison in Rome.

In 1599, while still in Venice, he published a treatise — The Way of Consolation and Helping the Sick to Die Well (Italian: Modo di consolare e aiutare gli infermi a ben morire) — and later was invited back to Naples.

The book was immediately popular, being republished nearly 60 times during Scupoli's lifetime and was translated into dozens of languages, including German, Latin, French, and English within ten years of its original publication.

[3] In the 18th century, Nicodemus the Hagiorite translated the book to Greek, adapting it for the benefit of Orthodox readers, and merging it with Scupoli's shorter Path to Paradise.