The histopathological evaluation of a testicular biopsy may be part of the diagnostic workup of andrological patients with azoospermia as well as men at risk for germ cell neoplasia in situ (GCNIS). In patients with azoospermia, the testicular biopsy is typically carried out at the same time as testicular sperm extraction (TESE). In this chapter, clinical indications for testicular biopsy in adult men are discussed. Technical issues related to the handling and processing of tissue samples as well as the use of immunohistochemical markers for different cell types and maturation stages are also briefly reviewed. Typical histopathological patterns associated with azoospermia and impaired spermatogenesis in andrological patients are described in detail and illustrated. Examples of GCNIS and other manifestations of testicular dysgenesis that can be encountered in a testicular biopsy are also presented. The review underlines the importance of testicular biopsy as a diagnostic tool.