Cryptic crossword clue
Terribly cute, on a bus, American gets under skin 12

The most common and most likely answer to this crossword clue is the 12 letter word SUBCUTANEOUS

I've seen this crossword clue in The Daily Telegraph
S
U
B
C
U
T
A
N
E
O
U
S

Buddy explains!

The straight part
We know that "under skin" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case under skin = subcutaneous.
The cryptic/wordplay part
In cryptic crossword there's often an wordplay/cryptic part as well.
This part involves a more complex hint, such as an anagram, homophone, hidden word, etc.
Sadly, We don't have an explanation for this specific crossword clue yet.

What does SUBCUTANEOUS mean?

SUBCUTANEOUS adjective
  1. Pertaining to the fatty layer under the skin.

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