Tyrosine kinase receptors Her2/neu and c-Met play an important role in breast cancer development and progression. In our study we determined the expression of c-Met, its ligand HGF/SF, and Her2/neu in ductal carcinoma in situ lesions of the breast (n=39) both by two different immunocytochemical techniques, classical immunohistochemistry and immunofluorescence and correlated their expression levels with histopathological and clinical characteristics. Both methods revealed similar c-Met staining patterns in the in situ component as well as the adjacent normal tissue (p<0.001). However, an imbalance in c-met expression between tumor and surrounding normal tissue was correlated with high-grade DCIS (Van Nuys Grade 3). No correlation existed between Her2/neu and c Met expression, indicating that both are not co-ordinately expressed in DCIS. High HGF/SF immunoreactivity was observed in 43.6% of the cases, yet, the adjacent cellular stroma revealed only low levels of HGF/SF. No correlation existed between c Met, Her2/neu, or HGF/SF expression and clinico-pathological factors. An imbalance in c-Met expression between tumor and surrounding normal tissue was associated with an aggressive DCIS phenotype. Moreover, c-met and HGF/SF may contribute to tumor development by different means than those controlled by Her2/neu.