Factual error: There is not a snowball's chance of Howard becoming an astronaut. He suffers from cardiac arrhythmia, something about which he is completely open. "Transient" or not this is easily detectable by a simple electrocardiogram, which is a fundamental part of the many medical examinations a potential astronaut will have to pass. He wouldn't even be allowed to start basic training. Note also that during his basic training he shows signs of severe stress and trauma which would inevitably trigger a cardiac episode. Even if it didn't the fact that he was falling apart at the seams would have him removed from the programme for his own good.
Factual error: Raj and Sheldon are watching TV in Raj's apartment and we hear music playing. Sheldon asks if the woman on TV was Aishwarya Rai to which Raj says yes and then they argue about her and Madhuri Dixit. The song playing was from the Bollywood movie Kaho Na Pyar Hai, but neither of them are in the movie - the lead actress was Ameesha Patel. (00:14:50)
Character mistake: In his conversation with Missy Sheldon makes it clear that his superior intelligence is a result of a random, mutated gene. Since Missy isn't similarly intelligent she obviously isn't carrying this mutated gene (which would be a billion to one shot anyway) so her offspring wouldn't inherit it. Sheldon would know this - his offspring would carry the mutated gene for superior intelligence, Missy's would not. Anyone knowing enough about genetics to use the term 'randomly mutated gene' understands enough to know that the mutated gene would only be expressed in a direct line from the carrier - Sheldon. Also bear in mind he has a model of the DNA molecule in his living room - it is obviously an interest.
Continuity mistake: When Howard is almost done moving out of his mother's house, there is a table in front of him with a measuring device in the top corner. In one shot, the device moves to the opposite corner of the table. In a few shots later, the item returns to its original position.
Plot hole: In Series 1, Episode 7, "The Dumpling Paradox, " Sheldon makes an oblique reference to his financial status: "Frankly, if I could afford the rent, I'd ask you [Leonard] to leave, " meaning he cannot pay the rent on his two bedroom apartment by himself - not that he doesn't want to, he can't. However, in "The Execlsior Acquisition, " we find that he does not even cash his pay cheques. He doesn't even deposit them into a bank account - he leaves them in a drawer in his desk. In Series 2 Episode 14 "The Financial Permeability", he lends Penny a large amount of money from a huge bankroll he just happens to have lying about - again, without cashing his pay cheques! He is obviously independently wealthy. Either he doesn't have enough money to afford the rent or he has enough to work without being paid while practically giving large amounts of cash away. Can't be both.
Factual error: Penny picks up a hand gun, pulls back the slide to ensure the chamber is empty and then releases it, leaving it closed. She then loads a magazine into the butt of the weapon and hands it to Leonard. He starts to smooch her and shoots himself in the foot. The gun could not have fired, because Penny would have to pull the slide all the way back and then release it again to load the first bullet. There couldn't have already been a bullet in the chamber, as the whole reason Penny pulled the slide part of the way back in the first place was to check just that.
Factual error: During the final scene of this episode, Sheldon steps out of his office wearing a gas mask and engages Leonard in conversation where he then states he is making hydrogen sulphide gas (more commonly known as H2S). Leonard correctly identifies this as highly flammable. However, this gas is far more dangerous and is harmful to the human body at as low a concentration as 20 parts per million (ppm), can cause permanent damage at 100ppm and is fatal after two breaths at 500ppm. So for Raj (and his bird) to be completely unharmed in a high concentration of H2S (noted by the fire) is impossible.
Character mistake: In his argument with Leonard regarding Superman's ability to fly, Sheldon states that in Superman 1, Lois Lane is two feet off the ground when Superman catches her as she falls from the helicopter. Not so. Superman catches Lois at least ten stories up. Additionally, both Penny and Sheldon say Superman "swoops down" to save Lois. Penny can be forgiven, but Sheldon would know better: Superman flies UP from ground level to catch Lois. (00:02:30)
Factual error: Sheldon says the movie Gremlins "baffles" him in regards to the instructions being very clear."Don't feed the gremlins after midnight." However, this instruction is only for caring of a Mogwai, not gremlins (the gremlins are formed by Mogwais eating after midnight). Sheldon, of all characters, would not mistake Mogwais for Gremlins and he would know the exact wording of the instructions.
Factual error: Sheldon and Amy have agreed to call each other "boyfriend" and "girlfriend." Sheldon suggests she should peruse the new relationship agreement while he sets up his notary stamp. As an agreement, both parties would sign. As a Notary, Sheldon would know that he could not notarize his own signature.
Character mistake: At the very beginning of the episode Leonard says "So you see what you're eating is not technically yogurt because it doesn't have enough live active acidophilus cultures." He is implying this is a scientific fact (he's not just giving his opinion on yogurt.) But to meet the U.S. standards for yogurt, only the starter cultures Lactobacillus bulgaricus and Streptococcus thermophilus are required, not Lactobacillus acidophilus. The presence or absence of L. acidophilus does NOT determine a food's identity as yogurt (which Leonard's line is implying). (00:00:05)
Continuity mistake: Sheldon is returning Amy's scarf and says, "You wore it the night we went ice skating, remember?" to which Amy replies, "You mean the night that I went ice skating and you stood at the rail Googling the symptoms of hypothermia." But in episode 8-12: The Space Probe Disintegration, Amy states that she cannot go ice skating because she has "unnaturally brittle ankles." (00:04:55)
Continuity mistake: When Howard is on the mound, the shot from behind the plate shows a player ready to catch the ball in a uniform shirt. The next long shot from the stands shows a catcher in full gear, and then back to behind the plate to the player in uniform shirt only.
Factual error: Sheldon tries to pretend that it is 2003, before he met Leonard. But in the episode The 21 Second Excitation S4 E8 it was stated Leonard and Sheldon waited in line for 14 hours to see the midnight premiere of Star Trek: Nemesis. Star Trek: Nemesis premiered on the 9th of December 2002.
Factual error: Sheldon's voice becomes squeaky when helium is pumped into his office. But if the room contained enough helium to make his voice squeaky just by breathing, Sheldon would actually be suffocating due to lack of oxygen, the lighter helium having displaced the heavier oxygen. You can do it with a balloon because you can breathe normal air between huffs, but if you're in a room full of helium, you won't last long before passing out and asphyxiating.