When I learned Spanish in school, I was taught to never say ¿Qué? when I needed someone to repeat something they just said. Rather I was taught to say ¿Cómo? Later, my wife taught me to say ¿Mande? as an even more polite question. But some people don't seem to understand what I'm getting at. Occasionally, they will try to clarify by saying "¿Qué?", which I'd always understood as rude. (Maybe I just look like a rude American or maybe the question isn't as disrespectful as I had learned.)
Am I safe in most situations (where I don't know the country of origin of the other speaker) in using ¿Cómo? (Trust me, this is a very common problem for me.)