In this context, proper histological grading, pathological staging (tumor size and lymph node status), as well as the assessment of predictive/prognostic biological features (ER, PgR, Ki-67, HER2) by IHC and ISH assays represent pre-analytical steps of multigene testing, engaging pathology labs to reshape the diagnostic workflow for ER + /HER2- eBC patients. This evidence concerns the gene ESR1 and neoplasm.