The frequency and pathogenesis of nodular regenerative hyperplasia of the liver (NRHL) were examined in general autopsy series. We found NRHL in 12 cases (2.1%) of 577 consecutive autopsy livers without hepatic necrosis, fibrosis, cirrhosis, or tumors. All of these cases were middle-aged to elderly adults, and there was a slight female predominance of 2:1. Symptoms related to the liver were absent in all but two cases. NRHL was an incidental finding in these 12 cases at autopsy. The main other diseases in these cases were classified into four groups: (a) organic cardiac diseases (four cases), (b) pulmonary diseases with right-sided cardiac hypertrophy (four cases), (c) small arterial diseases involving the liver (two cases), and (d) systemic amyloidosis involving intrahepatic small arterial branches (two cases). The frequency of NRHL in these four groups at autopsy was 3.8, 7.1, 33.3, and 22.2%, respectively, suggesting that while NRHL is rare, clinicians should be aware of its association or development of NRHL in several conditions. Disturbances of outlet venous blood flow and inlet arterial blood flow may contribute to the development of NRHL in the former two and latter two groups, respectively.