The book is set in the town of Hemlock Grove, Pennyslvania. The town is a mixture of extreme wealth and poverty, as the closing of the town's steel mill many years earlier caused many to lose their jobs. The town's main sources of employment are now the Hemlock Acres Hospital and Godfrey Institute for Biomedical Technologies. Run by the powerful Godfrey family, the Institute is rumored to have several sinister experiments take place within it on a daily basis. The town's rumor mill turns even more twisted when two teenage girls are brutally killed, their bodies left for unsuspecting people to find the next day. Peter Rumancek, a 17-year-old Romani, is suspected of the crimes by some of the townsfolk and is also rumored to be a werewolf. While he secretly is a werewolf, he isn't the actual killer and along with Roman, the heir to the Godfrey estate, sets out to find the killer.

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