The taxonomic attribution of isolated hominin distal humeri has been a matter of uncer-tainty and disagreement notwithstanding their relative abundance in the fossil record. Fourtaxonomically-based morphotypes, respectively representing P. boisei, P. robustus, non-erectus early Homo and H. erectus, have been identified based on the cross-sectional outershape variation of an assemblage of Plio-Pleistocene eastern and southern African speci-mens (Lague, 2015). However, the existence of possible differences between Paranthropusand Homo in the inner structural organisation at this skeletal site remains unexplored. Weused noninvasive imaging techniques to tentatively characterize the endostructural orga-nization of five early Pleistocene distal humeri from South Africa (TM 1517g, SK 24600,SKX 10924, SKX 34805) and Ethiopia (Gombore IB), which have been variably attributedto Paranthropus or Homo. While the investigated specimens reveal diverse degrees of innerpreservation related to their taphonomic and diagenetic history, in all but SK 24600 fromSwartkrans we could comparatively assess some geometric properties at the most distalcross-sectional level (%CA, Ix/Iy, Imax/Imin) and quantify cortical bone thickness topographicvariation across the preserved shaft portions by means of a 2-3D Relative Cortical Thicknessindex. Whenever possible, we also provided details about the site-specific organization ofthe cancellous network and measured the same parameters in a comparative sample oftwelve adult extant humans. For most features, our results indicate two main patterns:the first includes the specimens TM 1517g, SKX 10924 and SKX 34805, while the secondendostructural morphotype sets apart the robust Homo aff. erectus Gombore IB speci-men from Melka Kunture, which more closely resembles the condition displayed by our comparative human sample. Notably, marked differences in the amount and pattern ofproximodistal cortical bone distribution have been detected between Gombore IB and SKX34805 from Swartkrans. Given its discordant outer and inner signatures, we conclude thatthe taxonomic status of SKX 34805 deserves further investigations.