Topoisomerase II alpha (topo IIa) is an enzyme that in normal cells is expressed predominantly in the S/G2/M-phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo II alpha is both higher and less dependent on the proliferation state in the cell. To study the expression of topo IIa and the relationship between that expression-and other variables in cases of breast ductal invasive carcinomas, 50 fine-needle aspiration biopsies were performed from the same number of female patients, diagnosed cytologically and confirmed histologically after surgery. The same cases were studied immunocytochemically using monoclonal antibodies to topo IIa and Her2/neu (CB11) by the alkaline phosphatase method (APAAP). Topo IIa was found in 32 cases (64%) of the carcinomas studied. An overexpression between topo IIa and Her2/neu was found (p < 0.005). A relationship between topo IIa expression, histological grade and lymph node status (LNs) was also found (p < 0.005). Increased topo IIa expression seems to be related to an aggressive form of breast cancer featuring Her2 amplification and lymph node metastasis.