Society of Toxicologic Pathology has recommended mDF to fix testes since 2002. However, subsequent studies showed that false TUNEL-positive cells were observed in mDF-fixed testes. This study compared the effects of different fixation methods on histology and TUNEL staining in mouse testes. Results showedthat fixation for 24 or 36 h in mDF provided better morphologic details in untreated testes, but markedlyenhanced false TUNEL-positive staining. To optimize the fixation, testes were fixed using mDF for 6 hand then PFA for 18 h. Interestingly, fixation using mDF/PFA manifested better morphologic details, andrarely caused false TUNEL-positive cells in testes. Finally, we examined germ cell apoptosis in testesusing mDF/PFA fixation in cadmium-treated mice. As expected, cadmium triggered germ cell apoptosiswhich was well visualized in the mDF/PFA fixed testes. Taken together, mDF plus PFA fixation not onlyminimizes false TUNEL-positive cells, but also provides integrated morphologic details in testes.