CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. It exists as standard (CD44s) and variant (CD44v) isoforms which have been shown to be associated with metastasis in a range of tumors. Both CD44s and CD44v are found in normal respiratory epithelium and in non small cell lung cancers (NSCLCs). However, there isn't much information regarding their role in the metastatic process of NSCLCs. We examined the expression of CD44s in 30 NSCLCs using immunohistochemical techniques. Ten were non-metastatic (N0, M0), 5 were metastases to lymph nodes (N1, M0) and 15 were excised brain metastases. We found CD44s positivity in all non-metastatic tumors with varying degrees of expression, whereas 10 out of 15 metastatic tumors in brain and 3 out of 5 lymph node metastases were negative for CD44s. There was a statistically significant inverse relation between the CD44s expression and metastatic potential (P < 0.05). Our results support the hypothesis that diminished or lack of CD44s is the functional equivalent of CD44v which may be an accompaniment of enhanced metastatic potential. The value of CD44 in predicting metastatic behavior of NSCLCs remains to be established in a larger series.