Objective <p>This study compared the mechanical properties of the proximal humerus with intact cancellous bone against those with region-specific defects, to clarify the role of cancellous bone in load transmission.</p> Methods <p>Eighteen proximal humeral specimens were scanned via micro-CT, and bone mineral density (BMD) was quantified at the anatomical neck, surgical neck, and tubercle base. Specimens were divided into three groups (n = 6) by randomized block design: Group A (anatomical neck defect), Group B (surgical neck defect), and Group C (tubercle base defect). Each group underwent biomechanical testing under a 355 N axial load simulating arm abduction. Surface displacement and strain were measured before and after cancellous bone removal using digital image correlation.</p> Results <p>The anatomical neck had significantly higher trabecular density than other regions, especially medially and posteriorly. Intact humeri showed stratified displacement with strain concentrated at the anatomical neck. After cancellous bone removal, Group A showed a 46.95% displacement increase (<i>p</i> &lt; 0.05), mainly in medial and posterior regions, with elevated strain in the humeral head and anatomical neck. Group B showed no significant change, while Group C had a 10.72% displacement increase (<i>p</i> &lt; 0.05) on the anterior surface, with increased metaphyseal strain and reduced diaphyseal strain.</p> Conclusion <p>Cancellous bone in the anatomical neck and tubercle base is critical for stress distribution in the proximal humerus, showing greater biomechanical importance than that in the surgical neck.</p>