BACKGROUND: The clinicopathologic spectrum of warty dyskeratoma (WD) is not well characterized and the pathogenesis of this unusual lesion is still unclear. OBJECTIVE: We reviewed the clinical and histopathologic spectrum of WD and investigated a possible involvement of human papillomavirus (HPV) infection in onset of this lesion. METHODS: A total of 46 cases of WD were analyzed clinically and histopathologically. Polymerase chain reaction (PCR) analysis for HPV-DNA was performed in 13 lesions of WD. RESULTS: A total of 46 lesions of WD from 45 patients (M/F ratio, 1:1.8; mean age 59.8 years, median 61 years, age range 3-88 years) presented as solitary papules or small nodules on the head and neck (32 cases), trunk (9 cases), lower extremities (4 cases), and upper extremities (1 case). One patient had 2 lesions. No patient had clinical signs of Darier's or Grover's disease. Histopathologically on scanning magnification, lesions showed mainly 3 architectural patterns, namely, cup-shaped (29 cases), cystic (6 cases), and nodular (2 cases). In 9 cases, a combination of two of these morphologic patterns was observed. Characteristically, the epithelial component in all WDs displayed foci of acantholytic dyskeratosis. Variable features suggestive of follicular differentiation toward the infundibular portion of a normal hair follicle were also observed, including a focal contiguity to pilosebaceous units in most cases (63%), and the presence of small infundibular cystic structures in a subset of lesions (46%). The majority of lesions (83%) also revealed a hyalinized or fibrous stroma with intrastromal clefts. PCR analysis for HPV-DNA performed in 13 cases inclusive of all representative architectural patterns was negative. CONCLUSION: We conclude that WD shows a wider spectrum of morphologic features than previously recognized. Despite some histopathologic similarities to viral warts, WD is not a manifestation of HPV infection. On the other hand, the majority of these lesions display overall histopathologic features consistent with a follicular adnexal neoplasm. On the basis of this finding, we propose the alternative term follicular dyskeratoma to better reflect the distinctive features of this peculiar lesion.