Learn Portuguese (Portugal): O que queres dizer com isso?

In Portuguese, there isn't a single everyday verb that works exactly like the English "to mean" in this context. Instead, you use the expression querer dizer, which literally translates to "to want to say". Since queres is the casual "you" form of querer, queres dizer literally means "you want to say" but is the standard way to ask "you mean".

Why does the question start with "O que" instead of just "Que"?

When asking "what" as a standalone pronoun (meaning it isn't followed immediately by a noun), it is very common in Portugal to use o que (literally "the what") rather than just que. While both can be understood, o que is the most natural and common way to start this kind of question in spoken Portuguese.

The English translation says "by that", but doesn't "com" mean "with"?

Exactly! Languages often use different prepositions to express the same idea. In English, we ask what you mean "by" something. In Portuguese, the set phrase is always querer dizer com (literally, to want to say "with"). It is best to memorize querer dizer com as a fixed conversational chunk.

Could I use "aquilo" instead of "isso" to say "that"?

Usually, no. Portuguese has specific words for "this" and "that" depending on distance. Isso is used for things near the person you are talking to, which includes abstract things they just said. Since you are asking about their recent statement, isso is the perfect choice. You would use aquilo for something physically or temporally far away from both of you.