Paget's disease of bone is a localized disorder of bony resorption. The mechanism underlying the development of the disease remains controversial. There is substantial evidence suggesting a genetic basis for Paget's disease in some patients. A viral etiology of Paget's disease has been advocated. A further hypothesis implicating an immunological mechanism for this disease is based on growing evidence reviewed in the text. The presented case showed clinical and X-ray features typical of a very aggressive form of Paget's disease. We hypothesize that the extreme local aggressiveness of this case was secondary to the patient's concomitant immunosuppression due to an extended therapy following renal transplant.