The house fly, Musca domestica L., a relevant sanitary pest, is mainly controlled by insecticides. However, an inappropriate use of chemicals may induce resistance, treatment efficacy decline and environmental damages. We evaluated toxicity of some organophosphates, pyrethroids, spinosad and neonicotinoids by topical applications on adults of a M. domestica strain (OcRo) collected from an intensive chicken farm in Northern Italy, in comparison to a susceptible strain (s-DBF). The OcRo strain exhibited higher levels of resistance (RR50) to four pesticides in comparison to s-DBF. Spinosad and imidacloprid had very low RR50, thus were still efficient in OcRo control.We also tested resistance to pesticides in OcRo after topical applications of synergistic compounds. Hydrolases were involved in phosphorganic detoxification and cytochrome P450 monoxygenases in that of pyrethroids. These results indicate that OcRo strain is now multiresistant to organophosphates and pyrethroids, and this should be considered for an environmentally safe pest management.