CD44v adhesion molecules have been known to be related with carcinogenesis and metastasis of some human cancers including brain metastases of various origin. In this study, we demonstrated further that CD44v expression in brain metastases is extremely heterogeneous. Generally, v5/v6 is homogeneously expressed in the cell populations, while up-regulated v7-v10 could be usually found in a proportion of tumor cells, especially those close to necrosis, at the tumor border and with strong tendency of invasiveness. Our data thus suggest that heterogeneous CD44v expression may be determined not only by intrinsic nature of the cells but also by the surrounding micro-environment. Expression of multiple isoforms of CD44v may confer metastatic cells certain unique abilities, allowing them to localize, then to form metastatic colony in the brain.