Chromosomal and gene abnormalities are responsible for 15%-30% of male-factor infertility. This study aimed to determine stereological properties of seminiferous tubules in infertile men with Klinefelter syndrome (KS), Y chromosome microdeletions (MYC) and CFRT gene mutation (CFTR), and to compare them with obstructive azoospermia (OA) of non-genetic origin (control group). In this study, 33 biopsy samples of testicular tissue from 18 patients (three with solitary testis) with OA of non-genetic origin (control group), 18 biopsy samples of testicular tissue from 9 patients with KS, 28 biopsy samples of testicular tissue from 14 patients with MYC, and 6 biopsy samples of testicular tissue from 3 patients with CFTR gene mutation were analyzed. The total volume, surface and length of seminiferous tubules were significantly smaller in KS compared with MYC. All investigated stereological parameters were significantly smaller in KS and MYC, respectively, compared with CFTR and control group. There were no differences in the results of stereological analysis when comparing histological subgroups (Sertoli cell-only syndrome; mixed atrophy) inside KS and MYC groups, respectively. Qualitative histological analysis revealed significant impairment of spermatogenesis in KS and MYC, whereas testicular parenchyma was fully maintained in CFTR and control group. Spermatogenesis was most seriously impaired in KS. In conclusion, stereological analysis has a valuable role in the diagnostic procedure of male infertility, whereas qualitative histological analysis has a predictive value for the successful testicular sperm extraction.