In a prospective study, the glenohumeral joints of 51 patients (aged 60 or above) were examined, using ultrasonography. Twenty-two patients were suffering from characteristic polymyalgia rheumatica (PMR) symptoms. In contrast, 29 other patients initially had similar complaints, but were diagnosed as having elderly onset rheumatoid arthritis (EORA, rheumatoid factor negative) upon development of typical symptoms. Ultrasound examination revealed glenohumeral joint inflammation in 40.9% (9/22) of the patients with PMR and 65.5% (19/29) of the patients with EORA. A discrete symmetrical biceps tendon sheath effusion was found in only three patients and unilateral in six patients with PMR. In contrast, 12 patients with EORA presented a massive effusion of the biceps tendon sheath, in some cases combined with a bilateral subdeltoid bursitis, and an intraarticular (i.a.) effusion/synovitis. To summarize our results: an i.a. effusion/synovitis, subdeltoid bursitis and biceps tendon sheath effusion were more frequent in patients with EORA, with a predominate symmetry and signs for massive inflammation. The typical ultrasonographic result in patients with PMR was a unilateral inflammation of the glenohumeral joint with predominate discrete biceps tendon sheath effusion and, in comparison with the EORA group, with signs of a low grade inflammation. We conclude that the results of our prospective study might be helpful in the differentiation of PMR and a rheumatoid factor negative subgroup of EORA at the first time of manifestation where clinical overlaps can be observed. However, ultrasonography of the glenohumeral joints might be a good and helpful instrument of differentiation in both diseases.