PurposeThe aim of the present study was to assess the frequency of Y-chromosome microdeletions and C677T polymorphisms in the MTHFR gene in a sample of Egyptian men with nonobstructive azoospermia. Patients and methodsThis was a case-control study carried out using a PCR-RELP assay in 107 patients with nonobstructive azoospermia and 107 healthy fertile individuals who served as controls.Results Y-chromosome microdeletions were detected in 11 (10.3%) patients. There was no significant difference between patients and controls in the MTHFR C677T genotype distribution and allele frequencies (P = 0.507). Conclusion Y-chromosome microdeletions play an important role in the development of nonobstructive azoospermia and there is no evident relation between the MTHFR C677T polymorphism and development of nonobstructive azoospermia.