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Lois leaves the kids behind to go on a cruise with Peter, and a jealous Stewie vows revenge.  Stewie ends up sneaking on the cruise and kills Lois.  Back at home, Stewie tries to destroy all evidence of his involvement and Peter's friends think Peter did it.  A year later, when Peter goes on trial, an alive Lois emerges and points to Stewie as the murder.

Family Guy
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Family Guy Season 6 Episode 4 Quotes

Chris: But I haven't seen Mom since she took me back-to-school shopping.
(cuts to living room. Joe is dressed like Lois with make-up and clothes)
Joe: So sweetie, you ready to go get some new notebooks and protractors and slacks?
Chris: I want blue jeans.
Joe: (yelling) You're getting SLACKS!

Quagmire: That fat bastard murdered Lois! That son of a bitch; he's a killer like Bernie Getz! You know, the killer from the eighties. I used to do a bit on him back when I did stand-up.
(Flashback to a younger Quagmire on a stage)
Quagmire: Ah, what else is in the news? Oh, oh Bernie Getz. D-Did you hear this? This guy Bernie Getz shot a bunch of muggers on the subway. Wouldn't mind having him when I go see my mother in law. (Microphone whines) No, but really, New York City's a great place to live...if you're a COCKROACH!
Man in Audience: You suck!!
Quagmire: (Sadly) I know.