Ha you found it!

Yes, I was asking it as a semi-serious question, and would still love to hear your take on the old strange cliche.

But I very much appreciate that you were able to peg the quote. Husband and I were watching a Buffy marathon and I absolutely had to quote Willow, who cracked me up with that line. It's all in her delivery. (see 19:53 for the quote)

Sent you a tip just for being the first to find the exact quote, and post a video! Bravo.

But again, Best Answer is still a possibility if you'd like to reply with a semi-serious take on the whole sore thumb conundrum.

Thanks for the tip!
Regarding a more serious answer:
They do indeed stick out. Here are some examples:

Case 1: Soreness caused by significant bruising
A bruised thumb is often swollen and painful and stiff. Forcing it to curl towards your palm when you grip something can be difficult and painful a person thus afflicted may not move it in coordination with their other fingers. This could make it appear to "stick out" from the rest. If the nail turns black or falls off, this could also visual distinguish the thumb from the fingers and make a “stick out” in the eye of the observer.

Case #2: Severe Splinter (especially under the nail)
A small localized wound, especially if infected, can become much more noticeable if you move the thumb around. It can lead to a throbbing surge of pain with each heartbeat. People are likely to do their best to avoid this by minimizing thumb movement, even when the other fingers move in a coordinated effort.

Case #3: Broken thumb
Broken digits are often placed in a conspicuous rigid splint to allow bones to set naturally. They can cause the thumb to literally “stick out” by preventing coordinated movement with the fingers on the same hand. They can figuratively make it “stick out” by making the thumb look much different than the other fingers.

Case #4: Burned or Cut Thumb
Significant burns and cuts are often bandaged. Thumbs can be difficult to bandage unless they are completely wrapped. This wrapping can have an effect similar to a splint in Case #3, and both reduce mobility and increase visibility of the sore thumb.

Case #5: Dislocated Thumb
Dislocations can be extremely painful and lead to swelling. When recovering from a dislocated thumb, the victim will often minimize thumb movement to prevent stimulating the injured joint. As in several of the above examples, deliberately preventing the sort thumb from moving in normal coordination with the fingers can make it appear to “stick out” in the eyes of an observer.