The purpose of this research was to describe the changes in marker expression and histologic morphology following androgen deprivation in malignant and benign human prostates. Fourteen patients receiving pre-radical prostatectomy total androgen deprivation had pre- and post-androgen deprivation evaluation of marker expression and histologic morphology (both malignant and benign). Marker expression was significantly reduced for serum (p < 0.0001) and tissue (p < 0.004) PSA as well as bcl-2 expression (p < 0.008). There were significant histologic increases in vacuolization (p < 0.001), pyknosis (p < 0.04), fibrosis (p < 0.01) and lymphocytic infiltration (p < 0.008) in the malignant tissue. There were significant increases in squamous metaplasia (p < 0.0002), fibrosis (p < 0.0005), basal cell hypertrophy (p < 0.0005) and lymphocytic infiltration (p < 0.0002) in the benign tissue. Androgen deprivation therapy produces significant changes in marker expression and morphology in prostate specimens. At times these iatrogenic changes can be confusing. Clinicians and pathologists must be aware of these changes.