In the episode, Constance (Lois) was introduced as the fiancee of Dr. Watson (Brian), but in actuality, she was the lover of the villainous Professor Moriarty (Peter). She was part of Moriarty's plan to kill Queen Victoria (Chris), which had him killing prostitutes whose names begin with the letter "V," doing so as The Scottish Duke. Following his arrest by Sherlock Holmes (Stewie), Moriarty sent Constance to seduce Watson and become his fiancee. All the while, the evil Constance set up Moriarty's lackey (Carter Pewterschmidt) to pose as Moriarty and get killed by Holmes, and later brutally murders a prostitute named Veronica (Meg) in the same fashion as the Duke: placing bagpipes in the body post-mortem.
Veronica's murder brought Holmes out of a planned retirement, and in his investigation, he posed as a prostitute to search for the murderer. It was there that Constance was revealed, as she came out in a hooded cloak and wielded her knife at the phony hooker, only to become perplexed when she wasn't dying (due to the metal frame). After hearing Holmes' voice scream for Watson, Constance ran off, but Holmes heard the voice of the villainess and informed Watson that his fiancee is the killer. Watson revealed that she bought two tickets to Paris for their planned honeymoon, and after arriving there by boat and train, the duo found Constance and chased her all the way to the top of the Eiffel Tower.
The heel of Constance's shoe gets stuck on the floorboards, and after dislodging it, she ended up toppling over and hanging to the tower. During Watson's attempt to save Constance, the villainess stated that she did it for him (covertly referring to Moriarty), while revealing that she never cared for Watson. Holmes asked Constance who it was she was committing the murders for, only for Constance to cackle and claim that he (Moriarty) stated that Holmes would never figure it out and that he'd be victorious, right before she fell off the tower and to her death.
- Alex Borstein also voiced previous Family Guy villainesses Pearl Burton, Marla, and Deirdre Jackson, and also played hidden villainess Lily Bailey in the 2010 film, Killers.