The Cuprizone mouse model is widely used in studies on de- and remyelination. In the hands of different experimenters, the Cuprizone concentrations that lead to comparable levels of demyelination differ considerably. The reasons for this variability are unknown. In this study, we tested whether different Cuprizone formulations from different vendors and manufacturers influenced Cuprizone-induced histopathological hallmarks. We intoxicated male C57BL/6 mice with six Cuprizone powders that differed in their manufacturer, vendor, and purity. After five weeks, we analyzed the body weight changes over the course of the experiment, as well as the demyelination, astrogliosis, microgliosis and axonal damage by histological LFB-PAS staining and immunohistochemical labelling of PLP, IBA1, GFAP and APP. All Cuprizone formulations induced demyelination, astrogliosis, microgliosis, axonal damage and a moderate drop in body weight at the beginning of the intoxication period. In a cumulative evaluation of all analyses, two Cuprizone formulations performed weaker than the other formulations. In conclusion, all tested formulations did work, but the choice of Cuprizone formulation may have been responsible for the considerable variability in the experimental outcomes.