We hypothesized that invasive ductal carcinomas (IDCs) with large central acellular zones comprising necrosis, tissue infarction, collagen, and hyaline material on their cut surfaces are formed in association with myoepithelial differentiation of the carcinoma cells. To verify this, the expression of S100 protein, alpha-smooth muscle actin (alpha-SMA), and glial fibrillary acidic protein (GFAP) and keratin 14, which has been shown to represent the myoepithelial immunophenotype, was examined immunohistochemically in 18 IDCs with such central zones covering more than 30% of each tumor area, 18 IDCs without such areas as negative controls, and 10 metaplastic carcinomas as positive controls for myoepithelial differentiation. Expression of S100, detected with a polyclonal antibody, S100-alpha, S100-beta, alpha-SMA, GFAP, and keratin 14, was observed in 61%, 83%, 39%, 33%, 28%, and 39% of the IDCs with large central acellular zones, 17%, 44%, 6%, 6%, 0%, and 6% of the IDCs without such zones, and 80%, 70%, 50%, 100%, 80%, and 50% of the metaplastic carcinomas, respectively. We concluded that IDCs with large central acellular zones frequently contain carcinomas showing myoepithelial differentiation. Such histological and immunohistochemical features in IDCs would be expected to be clinicopathologically significant.