We recently described for the first time the presence of calcitonin immunoreactivity (CTIR) in a subpopulation of prostatic and urethral endocrine-paracrine (EP) cells. We now further evaluate the distribution of the CTIR cell, characterize the coexistence of serotonin and calcitonin, and for the first time describe the coexpression of calcitonin and other calcitonin gene family peptides (calcitonin gene-related peptide and katacalcin) in the CTIR cell. Finally, the morphological ultrastructure of the secretory granule of the CTIR cell is analyzed. The finding of multiple calcitonin gene family peptides in prostatic and urethral EP cells and the specific localization of calcitonin to secretory granules strongly suggest that the calcitonin gene is expressed in this region and the products stored in the EP cells. The relatively high levels of calcitonin reported in the semen and the dendritic and nondendritic morphological features of the CTIR cell, respectively, suggest a lumencrine (exocrine), paracrine, and possibly endocrine role for calcitonin. The production of calcitonin and related peptides by the prostate may have implications in various pathologic processes of the prostate.