In addition to its presence in the cytoplasm, heparanase was also noted to assume nuclear localization, demonstrated by cell fractionation,34 and by immunostaining of cultured cells34 and tumor biopsies.27,35 Interestingly, nuclear localization was correlated with maintained cellular differentiation35 and favorable outcome of patients with gastric27,35 and head and neck carcinomas,36 suggesting that heparanase is intimately involved in gene regulation. This evidence concerns the gene HPSE and neoplasm.