The association of xanthogranulomatous pyelonephritis and systemic amyloidosis is extremely rare. To our knowledge, despite innumerable cases of xanthogranulomatous pyelonephritis reported in the literature, this association has been described on only 2 occasions. Clinical, analytical and radiographic findings can be highly suggestive of the diagnosis. We report on 2 patients with xanthogranulomatous pyelonephritis, systemic amyloidosis and the nephrotic syndrome: 1 died 4 1/2 years after diagnosis and 1 was stable with good general health 3 years after diagnosis. The clinical aspects as well as the treatment given to both patients are discussed. We describe the natural history of an association that due to its rarity is not currently well known.