Melanoma in situ (MIS) of the penis is very rare in dermatologic literature. The standard of care for MIS is surgical removal by excision with a 5-mm margins or Mohs micrographic surgery. Nevertheless, surgery is occasionally not feasible for a number of reasons, such as patient comorbidities, potential aesthetic and functional impairment and patient preference. Recently, topical treatment with an immunomodulator, imiquimod, has been proposed as an alternative treatment for MIS. Dermoscopy, beyond its well established usefulness in the diagnostic evaluation of melanocytic lesions, has also shown to be an important tool in monitoring therapeutic response to various dermatoses. We present a case of a 38-year-old man who presented a MIS of the glans penis, histopathologically diagnosed, treated successfully using imiquimod.