Alpha-fetoprotein (AFP) has long been recognized and accepted in the clinic as a valuable tumor biomarker for liver and germ cell cancers. Correspondingly, AFP has also been utilized in combinations with other tumor markers for the diagnosis of breast cancer (BC). Over the last four decades, AFP has demonstrated only a lackluster contribution and limited value in utility as a member of various tumor marker assay combination panels for BC. This limited value in assay combination panels can be attributed to a lack of sensitivity and specificity in screening. It is approaching a time when AFP could possibly be deleted, without consequences, as a biomarker for breast cancer. Thus, the usefulness of AFP as a tumor biomarker for breast cancer should be re-evaluated and quantitively assessed in view of its 40 years of assay utilization in the cancer clinic.