Several premalignant and malignant neoplasms clinically appear as chronic eczematous lesions of the perianal region and have to be distinguished from benign processes. Anal intraepithelial neoplasia (AIN) presenting as bowenoid papulosis and perianal Bowen disease is a precursor lesion for invasive squamous cell carcinoma. When AIN is widespread, persistent or progressive, an underlying immunosuppression should get excluded. Verrucous carcinoma of the perianal region is a highly differentiated variant of squamous cell carcinoma characterized as a slowly growing but locally invasive tumor. Extramammary Paget disease (EMP) is an intraepithelial adenocarcinoma of the skin with apocrine differentiation. Along with EMP, basal cell carcinoma, Langerhans cell histiocytosis and cutaneous T-cell lymphoma should be included in the differential diagnosis for lesions simulating chronic perianal dermatitis. In such situations, biopsies and histopathologic examination are imperative to avoid delayed diagnosis and assure prompt therapy.