Leonard and Raj are walking the halls at the university. Leonard is mocking people who think that there is a danger of the Large Hadron Collider in Geneva, Swizterland creating a black hole which could end all life as we know it. Raj agrees that these people are "cry-babies". As they walk, they see a notice for a clinical trial for a drug designed to treat, among other things, social anxiety disorder (which would include Raj's selective mutism).They soon bump into Howard who is peeping into Sheldon's Office.
Leonard and Raj come around the corner to discover that half the university staff is hanging out outside Sheldon's office, because he's talking with a young woman - who turns out to be his twin sister Missy. Sheldon makes introductions and as usual, Raj simply walks away rather than talking to a woman by answering Missy when she forgets his name. Howard makes sure to point out that he's busy working on a project that might take him up on the next space shuttle mission. Missy is visiting California to attend a friend's wedding, and she has stopped by to have Sheldon sign some papers related to their father's estate. Sheldon thinks that his mother sent Missy to "visit" in order to spy on him. Leonard invites Missy to stay with them rather than make the drive to Anaheim in rush hour. Missy notes how Sheldon has always hated "company", even sending his imaginary friends home at the end of the day. Sheldon corrects her, in that they were imaginary colleagues, rather than friends.
At Apartment 4A, Missy tells the boys how, as an 8-year-old child in second grade, Sheldon converted her Easy Bake Oven into a powerful furnace, which burned off her eyebrows. Sheldon's defense is that he needed that high temperature to fire ceramic semiconductor substrates to make integrated circuits that he needed to build a defense robot designed to keep Missy out of his room. Missy laments that she had to draw on her eyebrows until they grew back.
Penny shows up with a pair of Leonard's Superman underwear, which Leonard claims he only uses for polishing his spear-fishing equipment (when he's not crossbow-hunting. Raj shows up and announces that he's in a clinical trial for medication to combat pathological shyness. He and Howard continue to converse with Missy, Raj pointing out that India is the home of the Karma Sutra and pajamas, while Howard points out that the Jews invented circumcision. Leonard gets defensive and feigns indifference. Seeing her discomfort, Penny invites Missy to the nail salon and they leave.
The three boys argue over who has standing to pursue Missy. Leonard gets sneaky and tells Sheldon he has to protect Missy's genetic integrity by only allowing someone suitable to fertilize Missy's eggs in order to potentially produce an individual as remarkable as Sheldon himself. Sheldon apparantly finds merit to this argument, as he storms out of the bedroom proclaiming that whoever wants to get at Missy's fallopian tubes will have to go through him!
They emerge from the bedroom to find Howard and Raj on the floor, putting each other in headlocks over Missy. Sheldon announces that none of them are good enough for his sister. Raj argues that his genes would bring genetic diversity, but Sheldon decides that Raj's need for pharmaceuticals takes him out of the candidate pool. Howard is too small and lives with his mother, and Leonard can't digest dairy products, so they too are out. Penny and Missy witness this conversation. [Missy: Oh, really?] Missy pulls Sheldon aside and reminds of how they handled conflict when they were little, and that she's prepared to reinstate those methods if he tries to interfere in her life. Sheldon emerges into the living room clutching his crotch and announcing that Missy can date whomever she wants.
With Missy now at hanging out at Penny's place, Howard, Leonard, and Raj decide to settle the battle over Missy the honorable way....via Wii boxing. Leonard triumphs over Howard (and presumably Raj) and heads to Penny's to share the news about his victory and the success of natural selection. He invites Missy to dinner, but she declines. Howard tries to be smooth, asking via magic trick, but is also rebuffed. Raj goes to make his invitation, but his medication is wearing off, and even though Missy is receptive, Raj chokes and ends up sulking away, defeated.
As Missy is leaving, she tells Sheldon that she is very proud of him, and brags to her friends about her brother the "rocket scientist". Sheldon is offended, wondering why she doesn't just tell them that he's a toll-taker at the Golden Gate bridge (a fitting reference, as Sheldon appears to have a particular fondness for the bridge - he has models and multiple prints of the bridge in his bedroom, including blueprints above his bed).
- Guest starring:
- Teleplay: Bill Prady & Lee Aronsohn
- Story: Chuck Lorre
- "The humor is pretty solid throughout and should entertain, even though there is a greater opportunity for character development wasted." - The TV Critic's Review
- IMDb user reviews.
- Title Reference: Howard expressed he would kill his Rabbi with a pork chop to be with Missy.
- Chuck Lorre's vanity card 
- This episode was watched by 7.38 million people with a rating of 2.8 (adults 18-49).
- Episode transcript 
- The original title for this episode, still used internationally in English-speaking territories, is "The Shiksa Indeterminacy".
- Second time that Raj is able to talk to a girl. Previously, it took a large dose of alcohol, while this time he using an experimental drug.
- In the beginning of the episode, Howard mentions a project he is working on that will take him up on the next space shuttle. This eventually happens in Season 5.
- Missy calls Sheldon by his nickname, "Shelly", just like their mother.
- Leonard says, "We don’t entertain much." This statement is similar to his statement in the "Pilot", "We don’t have a lot of company over." Yet, Sheldon made his resentment for such clear in that episode. It may be that he was implying that they (the four guys) do not entertain much (outside of their social circle) and thus have little idea how to be good hosts.
- In the pilot, Sheldon tells Leonard that his sister is a hostess at Fuddruckers.
- The only other appearance of Missy occurs when you can hear her screaming during childbirth in "The Cooper Extraction".
- Leonard, Howard & Rajesh sat in Sheldon's spot in some of the parts of this episode.
- Sheldon's twin sister, Missy, is in town for a wedding
- Leonard: If the wedding's not until tomorrow, why don't you stay with us tonight?
- Missy: Oh, I don't think so. Shelly doesn't like company. Even as a little boy, he'd send his imaginary friends home at the end of the day.
- Sheldon: They were not "friends". They were imaginary colleagues.
- Penny: So, Sheldon's sister is pretty cute.
- Leonard: I wasn't staring!
- Penny: I didn't say you were; I just said she was cute.
- Leonard: Oh! Uh, maybe... if you like women who are tall... and perfect.
- Penny: Sheldon, why are you ignoring your sister?
- Sheldon: I'm not ignoring my sister. I'm ignoring all of you.
- (Leonard wants to sleep with Missy, but Sheldon doesn't let him.)
- Sheldon: Here. Eat this cheese without farting and you can sleep with my sister.
- (Missy is leaving and Sheldon is saying goodbye to her.)
- Sheldon: OK, well, it was pleasant seeing you, other than that business with my testicles. (Puts his hand out for her to shake.)
- Missy: Come on, Shelly. (Gives him a hug, which Sheldon does as well.)
- Missy: I want you to know I'm very proud of you.
- Sheldon: Really?
- Missy: Yep. I'm always bragging to my friends about my brother, the Rocket Scientist.
- (Sheldon looks in disbelief.)
- Sheldon: You tell people I'm a Rocket Scientist?!
- Missy: Well, yeah.
- Sheldon: I'm a theoretical physicist.
- Missy: What's the difference?
- Sheldon: What's the difference?!
- Missy: Goodbye, Shelly.
- Sheldon: My God! Why don't you just tell them I'm a toll taker at the Golden Gate Bridge?! Rocket Scientist, how humiliating!
- Leonard: Sheldon, are you going to introduce us?
- Sheldon: Oh, alright, this is Missy, Missy this is Leonard and Rajesh and you’ve already met Howard.
- Missy: It’s nice to meet you.
- Leonard: You too, swell, also.
- Howard: Yeah.
- Leonard: So, how do you two know each other.
- Missy: Oh, he once spent nine months with my legs wrapped around his head.
- Leonard: Excuse me?
- Sheldon: She’s my twin sister; she thinks she’s funny but frankly I’ve never been able to see it.
- Missy: It’s because you have no measurable sense of humor, Shelly.
- Sheldon: How exactly would one measure a sense of humor? A humormometer?
- Missy: Okay, Shelly, sit down. Now I've lived my whole life dealing with the fact that my twin brother is, as Mom puts it, one of God’s special little people.
- Sheldon: I always thought I was more like a cuckoo bird. You know a superior creature whose egg is placed in the nest of ordinary birds. Of course the newly hatched cuckoo eats all the food, leaving the ordinary siblings to starve to death. Luckily for you, that’s where the metaphor ended.
- Missy: I thought it ended at cuckoo. Now you listen to me, if you want to start acting like a brother who cares about me, then terrific. Bring it on. But you try one time to tell me, who I should be sleeping with, and you and I are going to go round and round the way we did when we were little. Remember? (Sheldon hurriedly crosses his legs.)
- Missy: Okay. I’m not even going to ask why you’re pimping me out for cheese. But since when do you care at all about who I sleep with?
- Sheldon: Truthfully, I’ve never given it any thought, but it has been pointed out to me that you carry DNA of great potential.
- Missy: What on earth are you talking about?
- Sheldon: Let me explain. You see, I’m a superior genetic mutation, an improvement on the existing mediocre stock.
- Missy: And what do you mean mediocre stock?
- Sheldon: That would be you. But residing within you is the potential for another me. Perhaps even taller, smarter and less prone to freckling, a Sheldon 2.0 if you will.