Serum tumor marker CA15-3 is widely used in follow-up for assessment of breast cancer prognosis. The aim of this study was to evaluate levels among healthy females and patients, to assess differences with tumor stage and grade, and to determine the relationship with estrogen and progesterone receptor expression. One hundred and thirty six Jordanian females were enrolled in this study: Forty-five were healthy females; seventy-two were diagnosed with breast cancer and nineteen diagnosed with benign breast lesions. Elevated serum CA15-3 level was significantly observed among breast cancer patients (37.95±6.65) compared to both healthy (14.97±0.8) and benign females (12.30±1.55), but no significant association was detected between serum CA15-3 level and age of cancer onset, menarche age, menopause age, parity and BMI. Decreased CA15-3 level was significantly associated with hormone therapy and oral contraceptive consumption among breast cancer patients. Significantly elevated CA15-3 serum levels were found among grade II, III and stage II and III breast cancer females compared to normal healthy females. Elevated CA15-3 serum levels were also found among ER+/PR+(54.242±7.89) and ER+/PR- (37.08±8.22) compared to healthy control females.