Hi, Debra K,
Welcome to the forum. I don't know where you are coming from, but since you say you will be considering Madrid for the round trip, you should price out what they call the "multi city" fare (travel agents call it an open jaw fare, I believe, but on the websites it is multi city). I flew this year from US to Madrid to San Sebastián (the San Sebastián airport is actually in Irún, and it is about a 1/2 hour walk into town from the airport). and then Santiago to Madrid to US. The fare difference between what I did and a round trip to Madrid was about $200 and it saved me a LOT of time.
The other great thing about having this all on one ticket is that if my flight to Madrid from Santiago had been late and I missed my connection, the airlines would have to figure it out, not me. But not if you bought two separate tickets. A few years ago, I was in Madrid waiting for a flight to the US when a young woman came rushing up saying she had flown in from Rome on a separate ticket and missed her flight to the US on American and wondered if they would just put her on the next flight, which was my flight to Chicago. They were happy to do that but she was charged a one way fare, last minute price for the Madrid flight and then on to home. It was much more expensive than her RT flight to Madrid had been -- a cautionary tale, but something you don´t have to worry about if you just book one ticket with all these segments.