As was mentioned here before, you can look up words in Dictionary if you have your dictionary already up and running. But what if you don't? Here is a quick way to call the Dictionary.app from Safari.
Bookmark a web page; say this one that you're reading right now. Then go to your bookmarks and find the URL that you have just bookmarked. Replace the text under the Bookmark title with something relevant, like Dictionary, and the URL under the Address with dict:///. Now add your modified URL into the Bookmarks Bar, at the leftmost position.
Now hit Command-1, and there is your Dictionary. Simply start typing your query.
[robg adds: Command-1 works, for those who don't know, because Safari automatically assigns Command-1 through Command-9 to your first nine non-folder bookmarks.]
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