The protozoan parasite Histomonas meleagridis is a member of the family Monocercomonadidae in the class Trichomonada. Due to food safety concerns, currently no prophylactic or therapeutic drug against the parasite is licensed in the European Union. Benzimidazoles are antiparasitic drugs, and some of them are licensed for use in food-producing animals. Benzimidazoles act on beta-tubulin, and the beta-tubulin sequence allows predictions about the efficacy of benzimidazoles. In this study, we sequenced and analyzed a part of the beta-tubulin gene of five H. meleagridis strains and of Dientamoeba fragilis. In each Histomonas strain, three to five different sequences were found. No clustering of sequences from the same strain was recognizable. A phylogenetic tree based on the amino acid sequences of trichomonal beta-tubulin genes placed the histomonal sequences on a branch with D. fragilis, separate from Monocercomonas sp. and Tritrichomonas foetus. All histomonal amino acid sequences predicted a susceptibility to benzimidazoles. However, when we tested the efficacy of five benzimidazoles, namely, albendazole, fenbendazole, flubendazole, mebendazole, and nocodazole, on H. meleagridis in vitro, all tested drugs showed no efficacy, even though the concentrations tested were higher than the concentrations found to be effective against Trichomonas vaginalis and T. foetus by other investigators.