Objectives: The aim of this study was to assess the relationship between serum and saliva levels of cancer antigen (CA) 15-3 and to compare them between women with and without breast cancer. Study design: A case-control study was carried out on 61 women aged 28-69 years, including women with and without breast cancer (26 as part of the case study and 35 as part of the control group) conducted at the Emam Khomeini Hospital, Tehran University of Medical Sciences. CA15-3 levels were assayed in serum and unstimulated whole saliva by EIA. Unpaired t-test, one-way ANOVA and Pearson correlation were used as statistical analysis. Results: The salivary and serological levels of CA15-3 in the cancer patients were significantly higher (P <0.01) than the salivary and serum levels of healthy controls. They were also higher in stage 2 than in stage 1 in cancer patients. However, the saliva flow rate was significantly lower in the cancer patients (P <0.01). There was a significant positive correlation between serum and saliva CA15-3 concentration (r = 0.614) and also between serum concentration and saliva output of CA15-3 (r = 0.541). Conclusion: The results of the study suggest that salivary CA15-3 may have potential use in the initial detection of breast cancer in women.