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The effects of resin of podophyllin on lesions of condyloma acuminatum have posed problems to pathologists who sought to differentiate them histologically from squamous cell carcinoma in situ. The most striking histologic changes in lesions of condyloma acuminatum following application of resin of podophyllin occur within the first 48 hours. They are pallor of the epidermis secondary to both intracellular and intercellular edema, numerous necrotic keratinocytes in the lower half of the epidermis, and a marked increase in the number of mitotic figures there. Within the edematous papillary dermis, there is a scattered infiltrate of lymphocytes, histiocytes, and neutrophils. The absence of nuclear atypia, multi-nucleated keratinocytes, and dyskeratotic cells, and the presence of the orderly sequence of maturation of keratinocytes within the epidermis permit histologic differentiation of podophyllin-treated condyloma …