Optimal processing, handling, and sampling of prostatic biopsies, transurethral resections, and radical prostatectomy specimens ensure accurate diagnosis and staging. Prognostic factors derived from careful examination of tissue samples are critical for patient management, including cancer volume, extraprostatic extension, surgical margins, vascular/lymphatic invasion, and perineural invasion. This chapter addresses these important issues, including recent recommendations of a consensus panel of the International Society of Urologic Pathologists.