Nancy Drew goes on vacation to New Orleans with her best friend Bess Marvin. As a favor, Nancy stops to check in on Ned Nickerson's friend, Henry Bolet. Henry's last living family member, his great-uncle Bruno, recently died and left him responsible for settling the estate. As soon as Nancy arrives, she is knocked out by someone wearing a skeleton costume, and she soon discovers that Bruno Bolet was the proud owner of the "Whisperer", a crystal skull rumored to protect its holder from almost any cause of death except murder. When Bruno died, the skull was not found among the clutter of the Bolet manor. Nancy teams up with Bess to find the mystical artifact before it falls into the wrong hands.​