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. This evidence concerns the gene ERBB2 and breast carcinoma.