We surveyed histochemically detectable copper in various liver diseases with emphasis on chronic biliary disease (CBD) and venous outflow impairment. Using rhodanine, we graded copper accumulation in 298 liver specimens: venous outflow impairment (n = 64), CBD (n = 123), Wilson disease (WD) (n = 12), chronic hepatitis C (n = 32), steatohepatitis (n = 28), sarcoidosis (n = 15), cholestatic hepatitis (n = 12), and acute large bile duct obstruction (n = 12). Copper was detected in 39% of specimens; all had chronic liver disease. Copper increased with increasing fibrosis. CBD accumulated copper more frequently than other chronic diseases (except WD), both in early (61% vs 3%) and late (94% vs 59%) stages and in larger amounts. Rhodanine was positive in 73% of livers with CBD, 20% with sarcoidosis, 9% with chronic hepatitis C, and 7% with steatohepatitis. Copper was detected in 14% of chronic venous outflow impairment specimens; with 1 exception, stainable copper was absent in early stages but detected in 38% of cirrhotic livers. In conclusion, rhodanine helps differentiate CBD from other conditions, including venous outflow impairment; in the absence of advanced fibrosis, rhodanine positivity strongly favors CBD. In contrast, rhodanine positivity is nonspecific in cirrhosis, but the absence of copper in that setting excludes CBD.