Men with non-obstructive azoospermia exhibit different histopathologic syndromes in the testicle biopsy, varying from aplasia, Sertoli cell only syndrome, maturation arrest and hypoplasia. The genetic basis of these syndromes is discussed. We present the diagnostic testicle biopsies performed on 160 consecutive non-obstructive azoospermic patients, and these results were correlated with the findings after multiple bilateral treatment testicle biopsy. Each syndrome had to be reevaluated as for the presence of at least one focus of spermatogenesis up to the primary spermatocyte, round spermatid, elongating spermatid, elongated spermatid, or spermatozoa stages. The clinical outcome using donor sperm-IVF, spermatid or sperm intracytoplasmic injection is thereafter presented. A new prognosis based on the findings of this large clinical series coupled to results obtained with Y chromosome molecular screening is offered. Alternative treatments to donor sperm for men without spermatids are discussed.