If you have ever used the house as rental property, you will almost certainly have a depreciation recapture event with which to deal.
If the house has always been used as a second home (never "business property"), then the calculation is simple:
Selling Price LESS selling expenses LESS adjusted basis EQUALS gain (or loss). In your case, this would be long-term capital gain (taxed at more favorable rates than ordinary income).
You need to ensure that you factor in your basis adjustments, such as improvements made over the years, closing costs, and any casualty losses.