Pulmonary alveolar microlithiasis (PAM) is a very rare autosomal recessive disorder in which microliths are formed in the alveolar space. PAM is infrequently complicated by pulmonary hypertension, the cause of which is unclear. The author in this paper found that the pulmonary hypertension was caused by a marked decrease in pulmonary vascular beds. Here, an autopsy case of PAM with a marked cor pulmonale is reported. A 14-year-old woman was found to have an abnormal pulmonary shadow, but the cause was unclear. At 24 years, she was diagnosed with a diffuse pulmonary abnormal shadow. At 42 years, she was diagnosed with PAM by imaging techniques. Her condition gradually worsened and she had to be treated with oxygen. She died of respiratory failure at 54 years. An autopsy revealed severe PAM and marked cor pulmonale. The heart weighed 360 g and right ventricular thickness was 10 mm (normal, 2-3 mm). Microscopically, the alveolar space was diffusely filled with microliths, and heart failure cells were recognized. Bone formations were scattered. The alveolar walls showed fibrous thickening, and pulmonary arteries showed atherosclerosis. The right ventricle showed marked cardiac hypertrophy. Chronic severe liver congestion was noted. A morphometric analysis using CD34-stained specimens showed a marked decrease (one tenth) in pulmonary capillary beds (capillary number: 8.6 +/- 3.1 per image), compared with normal lungs obtained from two other autopsies (85.3 +/- 9.4 and 96.2 +/- 10,3). It was concluded that the cor pulmonale and pulmonary hypertension in the present case were caused by the marked decrease of the pulmonary arterial vascular beds. More research is required regarding the etiology and treatment of PAM.