We recently developed a malignancy-risk gene signature that was shown to identify histologically-normal tissues with a cancer-like profile. Because the signature was rich with proliferative genes, we postulated it might also be prognostic for existing breast cancers. We evaluated the malignancy risk gene signature to see its clinical association with cancer relapse/progression, and cancer prognosis using six independent external datasets. Six independent external breast cancer datasets were collected and analyzed using the malignancy risk gene signature designed to assess normal breast tissues. Evaluation of the signature in external datasets suggested a strong clinical association with cancer relapse/progression, and prognosis with minimal overlap of signature gene sets. These results suggest a prognostic role for the malignancy risk gene signature in the assessment of existing cancer. Proliferative biology dominates not only the earliest stages of tumor development but also later stages of tumor progression and metastasis.