OBJECTIVE To evaluate human epidermal growth factor receptor 2 (HER2/neu) interobserver variability between specially trained and untrained general histopathologists. METHODS The retrospective study cases of invasive breast carcinoma received at Shifa International Hospital, Islamabad, from June 2010 to December 2011, for assessment of HER2/neu status by immunohistochemistry which were retrieved from the files and, 30 consecutive cases each of score 0, 1+, 2+ and 3+ were selected for a total of 120 cases. Two groups of two histopathologists each examined the cases blindly. One group had attended a short course in Germany, while the other group comprised two qualified histopathologists who had not had any special training. Each histopathologist reported the cases independently according to standard guidelines. Kappa statistics were applied. RESULTS The trained group of histopathologists showed agreement in 113 (94%) cases. Kappa value was calculated to be 0.96 which means 'perfect agreement. In contrast the untrained group showed agreement in 83 (69%) cases with a kappa value of 0.59 which means 'moderate agreement. CONCLUSIONS Interobserver variability in immunohistochemical scoring of HER-2/neu in breast carcinoma is high among untrained general histopathologists. This may adversely affect the selection of patients with cancers who could benefit from Herceptin therapy.