Abstract: The role of parathyroid hormone-related peptide (PTHrP) in the regulation of hypercalcemia in patients with malignancies is well studied, but whether its expression in tumor tissue correlates with tumor progression is not clear at present. The majority of tumors that metastasize to the bone produce PTHrP, and PTHrP expression correlates with skeletal localization of tumors. About 95% of colorectal adenocarcinomas overexpress PTHrP mRNA and protein, and the expression level is higher in poorly differentiated than in well-differentiated adenocarcinomas. However, there is some controversy at present about the prognostic significance of PTHrP expression on primary tumor cells, and studies suggest that there might be tissue-specific responses. We will briefly present here existing evidences that suggest that the expression of PTHrP in the primary tumor tissue could have both positive and/or negative impact on tumor progression and clinical outcome of the disease.