CA15-3, a peptide derived from MUC-1, an hormonally-regulated protein, is the most widely used serum marker of breast cancer. CA15-3 level increases at the metastatic phase in 50-80% breast cancer patients. Although rise of CA15-3 precede symptoms of metastasis by a mean time of 2-9 months, current international guidelines do not recommend its routine use for screening for metastases because of moderate sensitivity and absence of clinical impact. We conducted a retrospective study among all patients with metastatic breast cancer seen by three senior breast oncologists during a 4-month period. We evaluated correlation of CA15-3 level at the time of metastatic relapse with ER, PgR and Her2 expressions, tumor type, size and nodal status at initial diagnosis, and sites of metastases. CA15-3 was increased in 168/272 patients (62%) at diagnosis of metastases. ER/PgR positivity was strongly correlated with elevated CA15-3 at this time (P < 0.0001). CA 15-3 was elevated in 69% of the cases of HR+ Her2- primary tumors at time of metastatic relapse. It was elevated in 56% of HR+ Her2+++, 46% of HR- Her2+++ cases and only in 41% of triple-negative cases (P = 0.003). these data confirm that CA 15-3 is very variably elevated at time of metastatic relapse of breast cancer, and this is dependant on HR status.