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Using single\u2010cell RNA sequencing, we identified and validated the <jats:italic>in situ<\/jats:italic> localization of three smooth muscle subtypes (prostate smooth muscle, pericytes, and vascular smooth muscle) and two novel fibroblast subtypes in human prostate. Peri\u2010epithelial fibroblasts (<jats:italic>APOD<\/jats:italic>+) wrap around epithelial structures, whereas interstitial fibroblasts (<jats:italic>C7<\/jats:italic>+) are interspersed in extracellular matrix. In contrast, the mouse displayed three fibroblast subtypes with distinct proximal\u2013distal and lobe\u2010specific distribution patterns. Statistical analysis of mouse and human fibroblasts showed transcriptional correlation between mouse prostate (<jats:italic>C3<\/jats:italic>+) and urethral (<jats:italic>Lgr5<\/jats:italic>+) fibroblasts and the human interstitial fibroblast subtype. Both urethral fibroblasts (<jats:italic>Lgr5<\/jats:italic>+) and ductal fibroblasts (<jats:italic>Wnt2<\/jats:italic>+) in the mouse contribute to a proximal <jats:italic>Wnt\/Tgfb<\/jats:italic> signaling niche that is absent in human prostate. Instead, human peri\u2010epithelial fibroblasts express secreted WNT inhibitors <jats:italic>SFRPs<\/jats:italic> and <jats:italic>DKK1<\/jats:italic>, which could serve as a buffer against stromal WNT ligands by creating a localized signaling niche around individual prostate glands. We also identified proximal\u2013distal fibroblast density differences in human prostate that could amplify stromal signaling around proximal prostate ducts. In human benign prostatic hyperplasia, fibroblast subtypes upregulate critical immunoregulatory pathways and show distinct distributions in stromal and glandular phenotypes. A detailed taxonomy of leukocytes in benign prostatic hyperplasia reveals an influx of myeloid dendritic cells, T cells and B cells, resembling a mucosal inflammatory disorder. A receptor\u2013ligand interaction analysis of all cell types revealed a central role for fibroblasts in growth factor, morphogen, and chemokine signaling to endothelia, epithelia, and leukocytes. These data are foundational to the development of new therapeutic targets in benign prostatic hyperplasia. \u00a9 2021 The Pathological Society of Great Britain and Ireland. 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