The most common and most likely answer to this crossword clue is the 4 letter word DOXY
I've seen this crossword clue in The Times
D
O
X
Y
Buddy explains!
The straight part
We know that "ancient mistress" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case ancient mistress = doxy.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 DOXY mean?
DOXY noun- A sweetheart; a prostitute or a mistress.
- A defined opinion.
- A broad-spectrum antibiotic, C22H24N2O8, of the tetracycline class.
- A dachshund.