The year is 1799 and Jacob de Zoet, a young clerk at the Dutch East India Company, intends to make his fortune. He plans to stay in Dejima (the man-made island where the Dutch traded with the Japanese) for a single year and earn his fortune so he can marry his fiancee Anna. However, while he is there, he meets an unusual young woman with a burned face by the name of Orito Aibagawa. The daughter of a Samurai and a midwife, she's studying medicine under Dr. Marinus and Jacob becomes quite attracted to her and Orito seems to reciprocate his affections.