Hercep Test (DAKO) is an immunohistological screening kit to select cases of advanced breast cancer with indication for treatment with a humanized mouse monoclonal antibody to human epidermal growth factor receptor-2, trasthzumab (Herceptin). We report a case of an 84-year-old female with invasive ductal carcinoma of the right breast, whose neoplastic cells showed a unique staining pattern in Hercep Test. The cells showed an intracytoplasmic fine granular staining pattern, instead of the membranous pattern of typical breast cancer cells. This unique staining pattern suggested some special features of the neoplastic cells. This case was finally diagnosed as invasive ductal carcinoma with focal neuroendocrine differentiation by subsequent imunohistochemical and electron microscopic examinations. The neoplastic cells showed positive reactivity for grimelius stain, chromogranin A, synaptophysin, and neuronspecific enolase, as well as electron-dense neurosecretory granules (up to 150 nm in diameter). This unique staining pattern of the neoplastic cells with Hercep Test is a useful clue to detect breast cancer with neuroendocrine differentiation, which is likely to be missed in routine examination. Clinical and pathologic findings including immunohistochemical and ultrastructural findings of this case are reported, together with a brief review of the literature.