HER-2 is over-expressed in around 25% of human breast cancers, and is associated with poor outcome. We examined the incidence of HER-2 status in inflammatory breast cancer (IBC). Forty-nine newly diagnosed IBCs were studied. Formalin-fixed paraffin-embedded pre-treatment tissue biopsies were examined immunohistochemically for the over-expression of the HER-2 protein and gene using the HercepTest and FISH assay. Clinical outcome was compared between the HER-2 positive (HercepTest score 3 + and FISH positive) and negative groups. Fifty-two per cent of the IBCs examined were HER-2 positive. The HER-2 positive group were demographically comparable to the HER-2 negative group. Ninety-six per cent of the HER-2 positive patients responded to primary chemotherapy compared to 76% of the HER-2 negative (P = 0.09). No significant differences in outcome emerged between the two groups. In conclusion, this study found the incidence of HER-2 protein over-expression in IBC is higher than previously reported in non-IBC. Early HER-2 directed therapy (such as the monoclonal antibody trastuzumab) as a part of multimodal treatment may improve outcome in this poor prognosis cancer.