Secondary pulmonary alveolar proteinosis (PAP) is rare but may occur in association with malignancy, certain infections, and exposure to inorganic or organic dust and some toxic fumes. This case report describes the second recorded case of PAP due to exposure to cotton dust. A 24-year-old man developed PAP after working as a spinner for eight years without respiratory protection. He was admitted as an emergency patient with very severe dyspnea for four months and cough for several years. Chest X-ray showed bilateral diffuse alveolar consolidation. He died 16 days later, and a diagnosis of acute pulmonary alveolar proteinosis was made at autopsy. The histopathology demonstrated alveoli and respiratory bronchioles filled with characteristic periodic acid Schiff-positive material, which also revealed birefringent bodies of cotton dust under polarized light. Secondary PAP can be fatal and present with acute respiratory failure. The occupational history and characteristic pathology can alert clinicians to the diagnosis.