Multiple breast cancer (MBC) is a controversial topic due to the lack of a consensus regarding its definition, classification issues and imprecise management recommendations in current reference guidelines. In four years, 756 patients with breast cancer (BC) were surgically treated in our Unit, 91 (12.03%) of them being pathologically diagnosed as MBCs. We present the results of our retrospective case-control study that performed a comparison between the clinicopathological characteristics and immunohistochemical (IHC) profiles of our MBC group versus a control group, represented by a sample of 184 cases randomly chosen from those with unifocal breast cancer (UBC). Starting from the premise of increased biological aggressivity of MBC, showed by several reports, we proposed to research the possible differences between these groups and to highlight their potential predictive and/or prognostic value. We found that MBC patients have a poorer prognosis than UBC ones - younger age at diagnosis [more cases less than 50 years old (p=0.03)], a lower frequency of T1 and a higher rate of T3 tumors [when using aggregate tumor size measuring method (p<0.001)], fewer node-negative (N0) cases (p=0.046) and a higher frequency of mucinous breast carcinoma (p=0.026). It worth mentioning that we obtained lower rates of poorly differentiated (G3) tumors (p=0.022) in the MBC group, this result being opposite to those found by other researchers. Our study also revealed a higher rate of human epidermal growth factor receptor 2 (HER2∕neu)-type cases in MBC group (p=0.022), these patients having the chance to benefit from treatment with monoclonal antibodies, with a better outcome than patients with triple-negative type. We registered significantly lower progesterone receptor (PR) positivity rates in patients with MBC, thus having a negative predictive value by showing a worse response to hormone-based therapies. Besides, we found heterogeneity of IHC features among tumor foci in MBC that may influence the therapeutic decisions. Our results sustain that MBC is biologically a more aggressive type of mammary neoplasia requiring a more particular therapeutic approach.