Androgen deprivation theraphy of the prostate induces a distinctive histologic pattern chracterized by cytoplasmic clearing, nuclear and nucleolar shrinkage, chromatin condernsation, and single-file infiltration resembling lobular carcinoma of the breast. Recognition of this variant may be difficult in needle biopsies and lymph node metastases because of its subtle infiltrative pattern and inconspieuous nucleoli. The authors evaluated the morphologic changes in prostatic adenocarcinoma after androgen deprivation therapy in a case—control study. Redical retropublic prostatectomies from 16 treated patients (flutamide and/or gonadotropin-releasing-hormone agonist) and 16 untreated control patients were matched for clinical state (all “I” 3) and posttreatment Gleason grade. Treated patients showed a significantly lower nuclear grade (grade on a 1—4 scale; P < 0.001) and smaller nucleolar diameter (morphometric analysis of 150 nucleoli from each case; P < 0.001) when compated with untreated control patients. There was no significant difference between the groups in frequency of aneuploidy or immunohistochemical expression of prostate specific antigen, prostatic acid phosphatase, S–10 protein, chromogranin, neuron-specific enolase, scrotonin, or basal cell–specific keratin.