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Background The pisiform and calcaneus are paralogous bones of the wrist and ankle and are the only carpal and tarsal, respectively, to develop from two ossification centers with an associated growth plate in mammals. Human pisiforms and calcanei have undergone drastic evolutionary changes since our last common ancestor with chimpanzees and bonobos. The human pisiform is truncated and has lost an ossification center with the associated growth plate, while the human calcaneus has expanded and retained two ossification centers and a growth plate. Mammalian pisiforms represent a wide range of morphologies but extremely short pisiforms are rare and ossification center loss is even rarer. This raises the question of whether the sole human pisiform ossification center is homologous to the primary center or the secondary center of other species. We performed an ontogenetic study of pisiform and calcaneus ossification patterns and timing in macaques, apes, and humans (n = 907) from museum skeletal collections to address this question. Results Human pisiforms ossify irregularly and lack characteristic features of other primates while they develop. Pisiform primary and secondary center ossification timing typically matches that of the calcaneus of non-human primates, while the human pisiform corresponds with calcaneal secondary center ossification. Finally, human pisiforms ossify at the same dental stages as pisiform and calcaneal secondary centers in other hominoids. Conclusions These data indicate that the human pisiform is homologous to the pisiform epiphysis of other species, and that humans have lost a primary ossification center and associated growth plate while retaining ossification timing of the secondary center. This represents an exceptional evolutionary event and demonstrates a profound developmental change in the human wrist that is unusual not only among primates, but among mammals.