The coincidence of systemic amyloidosis and xanthogranulomatous pyelonephritis has been reported previously only once. Clinical findings, such as the nephrotic syndrome, cardiac and autonomic nervous system dysfunction, and adrenal insufficiency, are suggestive and a thorough investigation to rule out other causes of secondary amyloidosis is warranted. We report a case of xanthogranulomatous pyelonephritis associated with secondary systemic amyloidosis and the nephrotic syndrome. Treatment consisted of nephrectomy and intensive supportive care. The unique clinical, radiographic and pathological aspects of this case are discussed.