Florid and widespread respiratory papillomatosis is a devastating disorder in a subset of patients with recurrent respiratory papillomatosis, and it poses a major dilemma for the patient and the surgeon. Contrary to common belief, the distribution of papilloma lesions is not random, but follows a predictable pattern, with lesions occurring at anatomic sites in which ciliated and squamous epithelia are juxtaposed. The predominant sites of disease in recurrent respiratory papillomatosis are the limen vestibuli, the nasopharyngeal surface of the soft palate, the midzone of the laryngeal surface of the epiglottis, the upper and lower margins of the ventricle, the undersurface of the vocal folds, the carina, and bronchial spurs. These sites have the common histologic feature of a squamociliary junction. Papillomata also occur at the tracheostomy tract and at the midthoracic trachea in patients with tracheostomies. At the latter sites, abrasion injury to ciliated epithelium heals with metaplastic squamous epithelium and creates an iatrogenic squamociliary junction. The apparent preferential localization of papilloma at squamociliary junctions has at least 2 implications: first, that detection of occult asymptomatic papillomata is enhanced by careful examination of squamociliary junctions, and, second, that iatrogenic papilloma "implantation" is preventable by avoiding injury to nondiseased squamous and ciliated epithelia.