Being aware that at present the need of a tailored treatment for EMPD is a critical clinical goal, but its concrete availability is still too far to achieve, we reviewed the current literature in order to study the impact of IHC expression in VPD and EMPD in both genders of biological markers that could serve as potential prognostic/therapeutic factors, including human epidermal growth factor receptor 2 (HER2/neu), Estrogen Receptor (ER), Progesterone Receptor (PR), and Androgen Receptor (AR). This evidence concerns the gene ESR1 and extramammary Paget disease.