+1 for the leakdown/compression test.
I had a #5 Misfire for a while (common, there are a bunch of threads on it). Replaced all the typical stuff thinking it was a simple tune up issue, bad wire, blah blah..
After the condition worsened and it was running rougher and rougher I did a compression test. #5 was WAY low, and when I put air on it I could hear air coming out the pipe, etc. Tore it down to find a nicely bent exhaust valve.
The moral of the story was that a new set of Magnum HD heads fixed *that* issue. Now I am backtracking a few other things, trying to find out what may have lead to it (ie, running lean due to a handful of things)
You can rent a comp. tester at Autozone and run it yourself. Screw it in the hole you think is bad (or all of them for complete confidence), unplug the coil wire and crank it over a few times. Take down your readings and see if you have 1 cylinder thats lower than the others by a significant margin.
I think mine averaged 130 or so on the "good" holes, and like 40 on the bad guy.