Nasal polyps are commonly associated with cystic fibrosis (CF) and also with idiopathic allergies, asthma, and aspirin intolerance. The pathogenesis of nasal polyp formation is controversial. The present study investigates the ultrastructure of thirteen nasal polyps surgically removed from seven CF patients and six non-CF (NCF) patients with allergic diseases, asthma, and aspirin intolerance. All nasal polyps showed focal edema, hyperplasia, atrophy, or squamous metaplasia of the epithelium. The lamina propria was moderately populated with small blood vessels and mucous glands and showed focal accumulation of inflammatory cells. The CF nasal polyps, however, revealed several specific characteristics: 1) minimal damage to the surface epithelium, 2) presence of a mucus blanket lining the apical epithelium, 3) occasional intracytoplasmic lumens, 4) continuous and fenestrated type capillaries, 5) numerous degranulated mast cells, 6) many plasma cells, often with atypical morphology and intracisternal Russell bodies, and 7) a smaller number of eosinophils as compared to the NCF nasal polyps. The results indicate significant differences between CF and NCF nasal polyps and support the multifactorial pathways theory of nasal polyp formation.