PAX8 is a specific marker for kidney, ovarian, and thyroid tissue. Antibody-dependent cross-reactivity for PAX8 has been reported in mesothelial, pancreatic, and B-cell proliferations. We recently described antibody clone-dependent aberrant PAX8 expression in breast cancer. In this study we systematically analyze PAX8 expression in breast cancer on whole tissue sections, using MRQ50 and BC12 PAX8 monoclonal antibodies. Immunohistochemistry was performed on formalin-fixed paraffin-embedded whole tissue sections from 85 invasive mammary carcinomas. Immunostaining was evaluated at ×10 objective; extent (intervals of 10%, 0% to 100%) and intensity (weak, moderate, and strong) of nuclear staining was evaluated in the tumor, benign breast tissue, and lymphocytes. With MRQ50 variable PAX8 nuclear positivity was identified in tumor cells in 35/85 (41%) cases. Of 35 PAX8 cases, 23 (66%) showed only weak expression in 1% to 10% cells, 8 (23%) were weakly (5/8) or moderately (3/8) PAX8 in 11% to 50% cells, and 4 (11%) showed weak PAX8 positivity in >50% tumor cells. All 3 (3.5%) cases that showed moderate nuclear PAX8 staining with MRQ50 were histologic grade 3. No PAX8 expression was noted in benign lobules/ducts with either antibody. Breast carcinomas can show nuclear immunostaining with MRQ50 PAX8 antibody with up to 3.5% cases showing moderately intense expression. The BC12 PAX8 antibody does not cross-react with breast carcinoma and lymphocytes. During workup of metastatic carcinoma, weak to moderate PAX8 nuclear expression with MRQ50 clone should be interpreted with caution.