I have usually seen that quotation in the modified form: "only two hard things: cache invalidation, naming things, and off-by-one errors". (It appears that this modification was introduced by someone called Leon Bambrick.)
I like the modified version because (1) it's funny and (2) off-by-one errors are indeed a common source of trouble (though, I think, in a rather different way from cache invalidation and naming things). I do wish Karlton had said "software development" rather than "computer science", though.
But that joke distracts from the original joke that caching is subsumed by "naming things."
If it's worth saying, but not worth its own post (even in Discussion), then it goes here.
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