OBJECTIVE: To explore toll-like receptor 2 (TLR2) immunolocalization and its possible role in the innate immune response against viral warts and molluscum contagiosum (MC). STUDY DESIGN: Using standard immunohistochemical techniques, we examined 50 cases (25 cases with viral warts and 25 cases with MC) together with normal skin biopsies of 25 age and sex-matched subjects who comprised the control group. RESULTS: TLR2 was expressed in the epidermis of all controls and in 94% of study cases. Staining patterns were cytoplasmic, membranous, nuclear and combined. There was a significant difference between cases and controls regarding the intensity (p = 0.0001) and pattern (p = 0.001) of TLR2 expression, where intense expression was in favor of cases and membranous and nuclear pattern of staining was seen only in cases. The intensity of TLR2 expression was significantly associated with patients of young age (p = 0.04), short disease duration (p = 0.04), facial location (p = 0.009), and MC category (p = 0.02). CONCLUSION: Our study suggests that upregulation of TLR2 is involved in the induction of defense mechanism against human papillomavirus and MC virus. Its nuclear localization may be related to virus pathogenesis, virus-TLR interaction, or to other unknown molecular events.