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If it's JUST misfiring on cylinders 5 and 3, run a compression test.
If the compression is down you'll need to remove the heads and inspect for damage or worn valves.
Since you didn't specify what kind of engine, I can only assume either a V6 or V8, and many "V" configuration engines have all even cylinders on one side and odd on the other.
If I can make an assumption, I would assume that the cylinders that are misfiring are adjacent to each other, giving a little more concern that it might be a failed head-gasket, but you won't know until the head is removed.
But again, check the compression first.
If compression is up across all cylinders, focus on electrical. Some engines used "coil packs" which caused a single coil to fire two cylinders. If that's the case you could have a problem with the coil pack or the electronics that fire it.
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