CD44 is a transmembrane glycoprotein and is regarded as a potential marker in various tumors. The aim of our study was to analyze the expression of the standard form of CD44 (CD44s) and its isoforms in localized prostate cancer (PCa), and to correlate these data with the classical prognostic factors and biochemical recurrence. Ninety-four surgical specimens were analyzed in this study. The expression levels of CD44s and all its 9 variants were analyzed by quantitative real time PCR (qRT-PCR). The control group consisted of 14 specimens from patients with benign prostatic hyperplasia. We correlated all the expression profiles with biochemical recurrence, as defined by a PSA >0.4 ng/mL in a mean follow-up period of 53.3 months. In PCa, CD44s was underexpressed and all the other isoforms were overexpressed. The mean expression level of most variants was higher in patients who had not recurred, and a higher expression of CD44v2 independently correlated with a better recurrence-free survival rate (p=0.045). This variant was also underexpressed in metastatic PCa cell lines. There was no correlation between the expression levels of any of the CD44 isoforms and the classical prognostic factors. We here demonstrated that PCa cases are characterized by a change in the expression of CD44, with a loss of CD44s and an overexpression of all the other CD44 variants. However, during cancer progression we found a loss of expression of all CD44 variants, and a correlation between higher expression of CD44v2 and a better recurrence-free survival rate. The understanding of the CD44 expression patterns in PCa could contribute to its use as a new prognostic marker.