Longitudinal rotation of the forearm (pronosupination) is an essential component of human manipulative tasks. The efficiency of this movement is dependent not only on the rotatory muscles but also on several morphological and structural features of the upper limb. In a recent study, we observed that the size and orientation of the humeral medial epicondyle played an important role in forearm rotatory ability. We further observed that the forearm muscular activity, specifically the motion of pronation, promotes radial curvature, which, in turn, enhances rotational efficiency. In this study, we aim to test whether the orientation of the medial epicondyle is an activity-dependent parameter or whether it is an invariable morphological feature characteristic of the human skeleton. We analysed the upper limb entheseal changes in 30 human skeletons and assessed the role of several functional groups in the anteroposterior and proximo-distal orientation of the medial epicondyle. Our results indicate that the orientation of the medial epicondyle is partially an activity-dependent feature basically determined by elbow flexor-extensors and hand and wrist flexors. The orientation of the medial epicondyle towards more posterior and proximal positions causes a gain of efficiency in the pronation range when the elbow is extended and in the supination range when the elbow is flexed. Therefore, we suggest that the medial epicondyle of the humerus is a structure involved in the manipulative capacities of the human upper limb, and its orientation presents a range of variation that may be associated with the functional enhancement of these abilities. Copyright © 2012 John Wiley & Sons, Ltd.