Behrens–Fisher problem
Yuri Linnik showed in 1966 that there is no uniformly most powerful test for the difference of two means when the variances are unknown and possibly unequal. That is, there is no exact test (meaning that, if the means are in fact equal, one that rejects the null hypothesis with probability exactly α) that is also the most powerful for all values of the variances (which are thus nuisance parameters). Though there are many approximate solutions (such as Welch's t-test), the problem continues to attract attention as one of the classic problems in statistics.
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Source: List of unsolved problems in statistics (CC BY-SA 4.0)