We examined the expression of CD44 isoforms in samples of breast cancer tissues from 95 patients by reverse transcription-polymerase chain reaction and immunohistochemistry, and tried to correlate the results with survival period. At the RNA level, expression of exon v2 was observed in 33 (35%) and that of v6 in 69 (73%) of the 95 specimens. Patients with CD44v2 mRNA expression had significantly shorter survival times than those with v2-negative tumors (P = 0.05), but there was only a weak correlation, if any, between v6 mRNA expression and overall survival (P = 0.06). Tumor tissue from 22 (23%) and 72 (76%) patients showed positive immunoreactivity with monoclonal antibody (mAb) M23.6.1. (CD44v2) and mAb 2F10 (CD44v6), respectively. Immunohistochemical evidence of CD44v2 peptide expression correlated with overall survival (P = 0.02), but there was no such association with CD44v6 expression in these tumors (P = 0.67). There were significant correlations between v2 immunoreactivity and higher histological grade and lower levels of estrogen and progesterone receptor. There was no significant correlation between v6 immunoreactivity and such clinicopathological characteristics. Although the expression of v2 was significantly associated with reduced overall survival, it was not an independent prognostic factor because it also correlated with progesterone receptor status. These findings suggest that v2 isoform expression might have more value than v6 expression for clinical use.