Introduction: Little is known about the biology, molecular profile and hence optimal treatment of African Nigerian breast cancer. The aim of this work, therefore, was to characterize the histology and molecular profile of Nigerian breast cancer. Methods: Breast carcinomas from women at 6 centres of similar tribal origin in Nigeria were reviewed and assembled into tissue microarrays (TMAs), and sections were stained for hormone receptors, i.e. estrogen receptor (ER)α, ERβ1, ERβ progesterone receptor (PR) and androgen receptor, cyclin D, HER2, Ki67 and cytokeratins (CKs), i.e. CK5/6 and CK14 (basal) and CK18 and 19 (luminal). Results: A total of 835 tumours were analysed. The mean age at diagnosis was 48.62 ± 12.41 years. The most common histological subtype was ductal NST (no-special-type) carcinoma (87.3%). Over 90% of the tumours were grade 2 or 3. The predominant molecular phenotype was the non-basal, triple-negative type (47.65%) followed by the HER2-positive group (19.6%). The percentage of ER-, PR- and HER2-positive tumours was 22.4, 18.9 and 18.8%, respectively. Conclusion: Nigerian breast cancer predominantly has a high-grade, triple-negative profile. It occurs at a younger age and bears similarities at the molecular level to pre-menopausal breast cancer in white women, with remarkably lower levels of ERβ expression. The early presentation and histological and molecular phenotype may explain the poor prognosis, and tailoring treatment strategies to target this unique profile are required.