Question: Do you think it's ok to change the signature of _PyType_Lookup() in this way by adding an error flag, or should I add a new function instead?

There is no performance difference to PR 3279 since gcc should optimise this flag properly away in most cases, so it's not a question about performance but about backwards compatibility. It's an internal, private function, which suggests that it should be ok, but it's not my decision. Cython calls it in a couple of cases, which I will obviously adapt in the next release, if the signature change is accepted.

Should the "no MRO after readying" error case be kept? It's the only non-exception error case, setting the error flag to 1. It seems ok to ignore this case, so it's not really an error, somehow. I would change it to return 0 (instead of 1), and thus change the error flag to simply "-1 on error (with exception set), 0 on success". Opinions?