The main aim of this study was to investigate putative correlation between the formation of prostate calcifications and the presence of cancer cells showing the ultrastructural and morphological aspects of osteoblasts. To this end, 40 prostate biopsies of prostate cancer were enrolled and investigated from histological, immunohistochemical, and ultrastructural point of view. To the best of our knowledge, this is the first study to propose a new cell type related to the ectopic calcifications in prostate tissue, the prostate osteoblast-like cells (POLCs). Although our data require further investigations about the molecular mechanisms of both POLCs Cells generation and calcification formation, this study can open new and interesting prospective in the management of prostate cancer patients. In fact, if our data will be validated in large-cohort studies, the presence of POLCs Cells and/or prostate calcifications could become a poor negative prognostic marker for cancer occurrence due to the correlation between the presence of POLCs Cells and epithelial to mesenchymal transition phenomenon.