B7-H4, a member of the B7 family, is involved in the regulation of antigen-specific immune responses. Its expression in a range of breast pathology and correlation to the number of CD3 and CD8 tumor infiltrating T-lymphocytes in invasive carcinomas were explored. The proportion of B7-H4 positive cells, staining pattern, and intensity were evaluated within diagnostic groups (normal and benign lesional, potentially premalignant and in situ carcinoma, and invasive carcinoma) on archival tissue blocks by immunohistochemistry. The proportion and intensity of B7-H4 expression was progressively increased across the major diagnostic groups. There was a significant association between a high proportion of B7-H4 positive cells in invasive ductal carcinomas and decreased number of tumor infiltrating lymphocytes (P=0.002). The cellular distribution of B7-H4 appears altered in the spectrum of normal to malignant breast. Its overexpression may help cancers avoid immune detection.