Purpose Most anthropometric data on the proximal humerus has been obtained from deceased healthy individuals with no deformities. Endoprostheses are implanted for primary and secondary osteoarthritis, rheumatoid arthritis, humeral-head necrosis, fracture sequelae and other humeral-head deformities. This indicates that pathologicoanatomical variability may be greater than previously assumed. We therefore investigated a group of patients with typical shoulder replacement diagnoses, including posttraumatic and rheumatic deformities. Material and methods One hundred and twenty-two patients with a double eccentrically adjustable shaft endoprosthesis served as a specific dimension gauge to determine in vivo the individual humeral-head rotation centres from the position of the adjustable prosthesis taper and the eccentric head. Results All prosthesis heads were positioned eccentrically. The entire adjustment range of the prosthesis of 12 mm medial/lateral and 6 mm dorsal/ventral was required. Mean values for effective offset were 5.84 mm mediolaterally [standard deviation (SD) 1.95, minimum +2, maximum +11] and 1.71 mm anteroposteriorly (SD 1.71, minimum −3, maximum 3 mm), averaging 5.16 mm (SD 1.76, minimum +2, maximum + 10). The posterior offset averaged 1.85 mm (SD 1.85, minimum −1, maximum + 6 mm). Conclusions In summary, variability of the combined medial and dorsal offset of the humeral-head rotational centre determined in patients with typical underlying diagnoses in shoulder replacement was not greater than that recorded in the literature for healthy deceased patients. The range of deviation is substantial and shows the need for an adjustable prosthetic system.