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.
| Name | Type | Role | |
|---|---|---|---|
| Gary Murphy | Writer | ||
| Jasmine Di Angelo | Guest Star | ||
| Josh Jacobson | Guest Star | ||
| Laurie Metcalf | Guest Star | ||
| Chanel Gaines | Guest Star | ||
| Tianna Danielle Kenney | Guest Star | ||
| Lyndsy Fonseca | Guest Star | ||
| Kate Lang Johnson | Guest Star | ||
| Abigail Mavity | Guest Star | ||
| Heather McPhaul | Guest Star | ||
| Montana Tsai | Guest Star | ||
| Alyssa Monka | Guest Star | ||
| Gracie Markland | Guest Star | ||
| Hayley Erin | Guest Star | ||
| Kevin Cooney | Guest Star | ||
| David D'Ovidio | Director |