Introduction Aim of this study was to determine the influence of clinical, histopathological and immunohistochemical parameters and the Nottingham prognostic index (NPI) on the occurrence of relapses compared with the HER-2/neu overexpression in breast cancer patients. Materials and methods In this study, 174 patients with primary breast cancer were analyzed in the period from June 2007 to June 2010. Clinical and histopathological parameters with the NPI, and additional immunohistochemical parameters were determined (HER-2/neu status, Ki67 and p53 protein product). During the follow-up period (42–80 months) relapses were observed in 38 patients (21.8%). Results The age of patients ranged from 28–83 years (mean 55.48+10.0). Positive lymph nodes were observed in 99 (57%) patients and in 70 (40%) patients; the tumor was poorly differentiated. HER-2/neu overexpression was observed in 33 (19%) patients, and in 13 (40%) of them, relapses were present. NPI was higher than 3.4 in 90% (30/33, HER2/neu positive patients) while HER-2/neu overexpression was associated with the tumor size, lymph-nodal status, mitotic index, degree of histological differentiation, lymph-vascular invasion, stage of the disease, Ki67, and p53 expression (p < 0.05). Conclusion NPI score is an excellent parameter to evaluate the course of disease in HER-2/neu positive breast cancer compared to occurrence of relapses. Aim of this study was to determine the influence of clinical, histopathological and immunohistochemical parameters and the Nottingham prognostic index (NPI) on the occurrence of relapses compared with the HER-2/neu overexpression in breast cancer patients. In this study, 174 patients with primary breast cancer were analyzed in the period from June 2007 to June 2010. Clinical and histopathological parameters with the NPI, and additional immunohistochemical parameters were determined (HER-2/neu status, Ki67 and p53 protein product). During the follow-up period (42–80 months) relapses were observed in 38 patients (21.8%). The age of patients ranged from 28–83 years (mean 55.48+10.0). Positive lymph nodes were observed in 99 (57%) patients and in 70 (40%) patients; the tumor was poorly differentiated. HER-2/neu overexpression was observed in 33 (19%) patients, and in 13 (40%) of them, relapses were present. NPI was higher than 3.4 in 90% (30/33, HER2/neu positive patients) while HER-2/neu overexpression was associated with the tumor size, lymph-nodal status, mitotic index, degree of histological differentiation, lymph-vascular invasion, stage of the disease, Ki67, and p53 expression (p < 0.05). NPI score is an excellent parameter to evaluate the course of disease in HER-2/neu positive breast cancer compared to occurrence of relapses.