Used to ask what something is or what is being referred to; asks for clarification about a topic or meaning.
「彼が怒っているって？」—「何のこと？」
"He's angry?" — "About what?"
メールに書いてある『問題があった』って、何のことか具体的に教えてください。
Please tell me specifically what you mean by "there was a problem" in the email.
その発言は冗談だよ。深刻に受け取る必要はないって、何のこと？
That remark was a joke. What do you mean by saying there's no need to take it seriously?
Refers to something out of the ordinary or unusual; can imply a suspicious or odd matter.
あの夜の騒ぎは一体何のことだったのか、町中で噂になっている。
People in town are gossiping about what that commotion the other night was all about.
彼の急な出張は何のことか分からないが、理由を聞いてみるつもりだ。
I don't know why he suddenly went on a business trip, but I intend to ask him the reason.
部長が急に機嫌を損ねた。何のことか心当たりがない。
The manager suddenly got upset. I have no idea what it's about.
An interjection expressing surprise or bewilderment — similar to "what the heck" or "what on earth".
え、給料が半分になったって？何のこと！冗談でしょ？
What — my salary was cut in half? What the heck! You're kidding, right?
そんなことを言うなんて、何のことだよ！信じられない。
Saying something like that — what on earth! I can't believe it.