Background: GATA-3 is a potential marker for detection of metastatic breast carcinoma, reportedly more sensitive than mammaglobin (MAM) and GCDFP-15. We aim to compare the sensitivity of GATA-3, MAM and GCDFP-15 in determining the breast origin of malignant effusions. Methods: Cell blocks from 27 cases of serous effusions positive for metastatic breast cancer were retrieved. Immunohistochemistry for GATA-3, MAM, gross cystic disease fluid protein 15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) was performed on cell-block micro-array. Statistical analysis using two ways Chi square, one-way ANOVA and multiple regression was performed. Results: The detection rate of breast cancer in serous fluid was significantly higher with GATA-3 (88.8 %, X2 = 15.9, p = 0.00034) than with MAM (51.8 %) and GCDFP-15 (37.0 %). All ER positive cases (19) were GATA-3 positive. Conversely, all GATA-3 negative cases (3) were ER negative. The intensity of stain and percentage of positive cells were significantly higher with GATA-3 (p < 0.0001) than with MAM and GCDFP-15. The intensity and percentage of positive cells score of GATA-3 were statistically associated with ER stain intensity and percentage of positive cell scores.