In the milestone 100th episode, ""Lois' Sister,"" Lois' younger sister, Susan (Laurie Metcalf), pays the family a visit and brings with her expensive gifts for the boys, biting remarks for Lois and a cold shoulder for Hal – whom she has never forgiven for dumping her for Lois. Lois and Susan's competitive relationship takes a turn for the worse when Susan gives Malcolm and Reese her prize '65 Mustang convertible. But when Lois discovers that Susan needs a kidney transplant, she puts her anger aside and offers to donate her kidney to Susan, which Susan only sees as the perfect opportunity for Lois to one-up her.
Elenco: Bryan Cranston , Justin Berfield , Erik Per Sullivan , Jane Kaczmarek , Christopher Masterson , Frankie Muniz , Craig Lamar Traylor , David Anthony Higgins , Emy Coligado , Eric Nenninger , Kenneth Mars , Evan Matthew Cohen , Kyle Sullivan , Gary Anthony Williams , Jennette McCurdy , Emma Stone , Cloris Leachman , James Rodriguez , Lukas Rodriguez .