The proinflammatory cytokine tumor necrosis factor alpha seems to play a major role in the pathogenesis of both rheumatoid arthritis and primary biliary cirrhosis. We describe the case of a 46-year-old female patient with rheumatoid arthritis and concomitant primary biliary cirrhosis treated with anti-tumor necrosis factor alpha agents. During infliximab treatment we observed a poor clinical response and persistence of liver function test abnormalities. After infliximab interruption the levels of alkaline phosphatase dropped and had nearly reached normal values when etanercept was started. This new therapeutic regimen was well tolerated with joint clinical improvement and normalization of alkaline phosphatase. This single case shows that etanercept therapy maintained liver enzymes within the normal range and controlled the arthritis with a 30-month follow-up whereas infliximab did not account for similar results.