Background: CD44, a major cell surface receptor for hyaluronic acid, is a family of ubiquitous cell surface glycoproteins. Altered levels of CD44 expression, seen in many epithelial neoplasms, have prognostic implications. Expression of standard and variant isoforms of CD44 was assessed in normal and neoplastic human prostate tissue and culture cells to evaluate as a marker for malignant transformation. Methods and Results: Expression of CD44s, CD44R, v5, v6, v7/8 and v10 was assessed in prostate tissue (benign and malignant) and cell lines (DU-145, PC-3, LNCaP, p69) and primary cultures of normal prostates and adenocarcinoma cells obtained from prostatectomies using reverse transcriptor polymerase chain reaction, Western blotting, and immunofluorescence. No CD44 expression was seen in LNCaP cells. p69, DU-145, and PC-3 cells expressed CD44s and CD44R. p69, cells demonstrated a 1000-bp-long form of CD44 mRNA, unique to this normal cell line. Both normal and neoplastic prostatic tissue demonstrated CD44s on Western blotting. Conclusions: In agreement with previous studies, prostatic adenocarcinoma cells, except LNCaP, expressed CD44s. Different patterns of CD44 expression were seen in benign and neoplastic prostate. Benign prostate exhibited higher v5 protein levels, whereas neoplastic prostates demonstrated higher CD44s expression. CD44s expression was identified in all neoplastic prostates as compared with only 50% of the benign prostates. No significant difference in expression of the other variants assessed (v6, v7, v7/8, and v10) was observed in the benign and neoplastic prostates.