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The clinical findings in cirrhosis and systemic amyloidosis may be similar, leading to difficulties in diagnosis. We studied three patients with systemic amyloidosis with a 99mTc sulfur colloid liver-spleen scan. In all three patients, uptake by the spleen was less than the liver, in contrast with the increased splenic uptake seen in patients with cirrhosis. The liver-spleen scan may be a useful tool in differentiating patients with cirrhosis from those with systemic amyloidosis when clinical findings fail to give the proper diagnosis.