Aberrant tumor cell expression of B7-H3, a member of the B7-family that stimulates interleukin-10 (IL-10) secretion, contributes to tumor immune evasion and tumor progression. The aim of this study was to investigate the expression of B7-H3 and IL-10 in ductal and lobular breast cancer tissues. Using immunohistochemistry, B7-H3 and IL-10 protein expression in tumor specimens of primary human breast cancer was investigated. The association between B7-H3 or IL-10 expression and clinicopathological variables was analyzed. The correlation between the expression of B7-H3 and IL-10 was also evaluated. In tumor tissues, the expression of B7-H3 and IL-10 was identified on the cell membrane and in the cytoplasm. Expression of B7-H3 was observed in 90.60% (106/117) of the specimens and 80.34% (94/117) expressed IL-10. Patients with a positive B7-H3 or high IL-10 expression were more likely to have positive lymph node metastasis (N1-3; P=0.018 or 0.035, respectively) and advanced disease (stage II-IV; P=0.011 or 0.039, respectively) compared to those with a negative or low expression. Furthermore, B7-H3 expression was correlated with IL-10 in tumor cells (R=0.545, P=0.000). High B7-H3 expression in human breast cancer tissues may be important in tumor progression and invasiveness. This expression appeared to be correlated with the ability of B7-H3 to promote IL-10 secretion.