Genetic defects are one of the most common causes of male infertility, apart from anatomic, endocrine and immunologic problems, and are estimated to be present in approximately 30% of infertile men. Genetic aberrations causing infertility are divided in three different types: chromosomal abnormalities, submicroscopic deletions and single gene defects. Aberrations of sex chromosomes, Y chromosome microdeletions in the Azoospermia Factor (AZF) regions and mutations in the Cystic Fybrosis Transmembrane Conductance Regulator (CFTR) gene have been clearly correlated with defects in spermatogenesis and are often tested as a possible cause of infertility. This study has encompassed 256 men diagnosed with infertility. Cytogenetic analysis and Y chromosome microdeletion testing were performed in all subjects. In addition to this, 33 men were tested for the presence of CFTR gene mutations. Chromosomal aberrations were detected in 21 patients (8%). In 29 patients (11%) at least one Y chromosome microdeletion was detected. Of 33 patients tested, CFTR mutations were detected in 6 men (18%). Etiology of infertility could be explained by presence of analyzed genetic changes in 55 men (21%). Mutations in the CFTR gene were very frequent in group of analyzed patients, suggesting that CFTR gene mutation analysis should be routinely performed in infertile men. It is proposed that at least in some cases which remain unexplained there is another genetic cause underlying infertility and therefore potential role of other genes should be investigated.