In the past, several EMPD studies have focused on investigating the HER2–PI3K/ERK signaling in EMPD because it is characterized by the presence of Paget cells, large round, vacuolated, pale-staining cells, as mammary Paget’s disease (MPD) and the clinical success in targeting aberrant receptor tyrosine kinase signaling pathways in breast cancer. The gene discussed is PIK3CA; the disease is extramammary Paget disease.