TV's most affable amnesiac is back, and she is, I suppose you could say, "forgetter than ever." But what exactly is new with ABC's Samantha Who? Melissa McCarthy, who plays Dena, the angel on Sam's shoulder (to Jennifer Esposito's gin-swilling devil), shared with us a peek at Season 2's possible catfights and very special guest stars. Plus: McCarthy hails series lead Christina Applegate as "a tough cookie" who didn't let breast cancer get the best of her.

TVGuide.com: What is going on with Dena this season?
Melissa McCarthy: I don't know a lot, but I'm curious to see what happens with Chase, her boyfriend. That's seems to be getting progressively weirder and funnier to me. Personally, I'm wondering if they're ever going to let us know what Dena does for a living. Every time I ask a writer, they just laugh. I don't know what that means! [Laughs] I've pitched that she's a parole officer, just so I could use mace or a Taser.

TVGuide.com: Now that we've established Samantha's amnesiac situation, would you say there is a different theme this season?
McCarthy: Yeah, now that that's set up, it loosens you up. You can have fun storylines and not worry about people not following it. Everyone knows these people are odd, and you can get away with more. Also, Samantha's not going to be working at her job anymore, and that opens up a whole new area, as for what she's going to be doing and whether we go along with her.

TVGuide.com: Will we ever get a meaty throw-down between Dena and Andrea?
McCarthy: Listen, you have no idea how many of those I've pitched. I've said it could be a little ode to Dynasty, with a fountain that appears out of nowhere. I bring up Tasers about once a show, so maybe we can get into a Taser fight? Have you ever talked to Jennifer Esposito? She's crazy. She would be up for anything, so I'm hoping we get a full-blown fistfight with punches to the face.

TVGuide.com: It was a riot last season when Dena and Sam's mother (Jean Smart) did each other's makeup.
McCarthy: Yes! [Laughs] Jean is so funny. I have a big picture of her and I in that full glamour makeup, and we both look like drag queens. Scary!

TVGuide.com: The show has lots of fun guest-stars coming up – like Mary-Kate Olsen, James Tupper (Men in Trees), and Anthony Anderson (Law & Order). Will you be working with any of them?
McCarthy: I worked with Mary-Kate and she was really sweet. Tony Hale, who plays Sam's neurologist, I just find him funny even when I'm not supposed to.

TVGuide.com: Did you manage to catch him on Andy Barker, P.I.?
McCarthy: Oh my god, yes. Tony's so good in everything he does. He's always perfectly odd enough that you're just a little uncomfortable.

TVGuide.com: Mary-Kate plays a bad girl that Sam tries to reform?
McCarthy: Yes – and it doesn't really work out that well! She did a good job with the part.

TVGuide.com: Christina Applegate really soldiered on through her cancer scare, at least on the surface, with nary a blink. Did that keep the mood on the set from ever being sad and more about empowerment and positivity?
McCarthy: Everything Christina does is about positivity. She's a real workhorse. And really, only a few of us knew and that was it. She didn't want it to bring down the set or interrupt work. She's a tough cookie, and she's doing great. She was smart, she caught it early. In all areas, she did the right thing.

TVGuide.com: You can only hope that a big takeaway from this is the importance of catching it early.
McCarthy: I've had quite a few people tell me that they are now going in early for a checkup. When you think about how many people might now get checked early, that's amazing.

TVGuide.com: Did Gilmore Girls leave you with any burning questions?
McCarthy: I want to know what the last line is! [Series creator] Amy [Sherman-Palladino] knows, though in the back of my head I sometimes think, "Does she really?" But I know she probably does.

TVGuide.com: Lastly, what would people be surprised to know about Melissa McCarthy?
McCarthy: That I have, like, 100 wigs.

TVGuide.com: To what end?!
McCarthy: For Groundlings, the improv theater. I wear them on-stage, and they're all mostly hideous. Bad short perm wigs, some mullets in there. Mostly it's the 55- to 60-year-old Midwestern woman hairdo. I have a strange amount of those!