Estrogen receptor (ER)-negative breast cancers are a group of tumors with poor prognosis and fewer cancer prevention and treatment strategies compared to ER-positive tumors. The aim of this study was to assess the morphological characteristics and immunohistochemical profile of ER-negative tumors and thus to understand the biological behavior and unique nature. In total, 291 consecutive ER-negative cases available from our primary breast cancer series were examined. Hematoxylin- and eosin-stained sections of all the cases were studied for several morphological parameters and their immunophenotype profile. These findings were correlated with patient and tumor characteristics and survival data. ER-negative tumors constituted 30% of the primary operable breast cancer series. The majority of tumors were grade 3 (94%) and the commonest histological types were ductal/no specific type (85%), and atypical medullary carcinoma (8%). High-grade comedo-type necrosis, lymphoid stroma, central necrosis/fibrosis and pushing margins were the most common morphological features. The presence of a pushing margin showed a significant relation to androgen receptor negativity, absence of epidermal growth factor receptor expression and negative lymph nodes. Lymphoid stroma and comedo-necrosis correlated with higher tumor grade. ER-negative breast cancers are a distinct group of tumors with several common morphological features. Grade 3 histology, pushing margin, lymphoid stroma, comedo-type necrosis and central fibrosis/necrosis are the dominant morphological findings. The presence of a pushing margin appears to have a significant correlation with negative lymph node status. ER-negative tumors show a higher expression of p53, CerbB2 and epidermal growth factor receptor compared to ER-positive breast cancer. These unique features support the concept that ER-negative tumors are a morphologically and phenotypically distinct entity and provide a rationale for the study and use of newer promising agents in the treatment of ER-negative breast cancer.