Medullary carcinoma of the breast has a relatively favorable prognosis despite its malignant histopathological appearance, providing a challenge for the pathologically based diagnosis of breast cancer. Macroscopic and microscopic findings combined provide diagnostic criteria. The importance of the immunophenotype of medullary carcinoma is not well defined. Because the reproducibility of morphological criteria is limited, we conducted an immunohistochemical study in search of markers that could facilitate histopathological classification. We examined 32 medullary carcinomas in comparison with 30 high grade ductal invasive carcinomas with similar morphology using 23 different immunohistochemical markers. The results showed an overlap with the so called basal like subtype of invasive breast cancer (negativity for steroid hormone receptor, positivity for basal cytokeratins). None of the immunohistochemical markers enabled a specific discrimination between the two groups. Medullary carcinomas overexpress EGF-R more frequently (P<0.004). In combining the characteristic morphological criteria and the immunohistochemical detection of the basal like phenotype and EGFR, a higher diagnostic accuracy can be achieved. The immunophenotype alone does not allow a definite classification of medullary carcinoma.