Heparanase is a glucuronidase that appears upregulated in many human cancers and is involved in cellular invasion and tumor metastasis. Heparanase 2 is a homologue of heparanase that lacks enzymatic activity and displays anti-metastatic features. The aim of this work was to analyze the expression of both molecules in neuroendocrine tumors. We investigated the transcription of heparanases in lung neuroendocrine tumors well- and poorly differentiated using RT-PCR, and the expresion of the proteins by means of immunohistochemistry. The tumors were selected according to different malignancy WHO 2013 grades and were arranged in tissue arrays. The prometastatic enzyme heparanase appeared overexpressed in well- but not in poorly differentiated tumors, irrespective of their location. Moreover, the anti-metastatic heparanase 2 increased its expression in well-differentiated tumors, but strongly decreased in poorly differentiated ones, again independently of anatomic origin. Given the involvement of both molecules in tumor progression, through both their catalytic and non-enzymatic properties, there would seem to be a relationship between the regulation of their expression and the features of the neuroendocrine tumor.