Simple SummaryBubalinoculture is a growing industry worldwide, and the commercialization of buffalo leather is rapidly expanding due to its thickness, weight, and flexibility compared to bovine leather. However, dermatological diseases in buffalo, such as leucoderma, are becoming increasingly common, particularly in the Amazon biome, resulting in significant economic losses due to the inability to utilize the leather. This study is the first to investigate and describe the epidemiological and clinicopathological aspects of leucoderma in buffalo in the Amazon biome, as well as to propose solutions to this problem in the region. The samples showed that there is no predisposition by breed, sex, or age for the occurrence of leucoderma. Regression of the clinical signs of acromotrichia and skin depigmentation occurred after a correct mineral supplementation of the animals, which is crucial for animal production systems. Mineral deficiency, particularly copper, is a significant predisposing factor for the occurrence of leucoderma in buffaloes in the Amazon biome. Therefore, the mineralization of buffalo herds is a continuous prophylactic practice that should be adopted by farmers afflicted with this problem.AbstractLeucoderma is a condition that affects the skin and hair of animals, causing depigmentation and acromotrichia. In buffaloes, this condition results in significant economic losses for the production chain due to its impact on the leather trade. This study aimed to investigate the epidemiological and clinicopathological aspects of leucoderma in buffaloes in the Amazon biome and describe the prophylactic treatment to control the disease. The study included 40 buffaloes, 16 males and 24 females, aged between 1 and 10 years, and were of the Murrah, Jafarabadi, Mediterranean, and Murrah × Mediterranean crossbreed breeds. The animals were raised without mineral supplementation. The clinical signs observed in the animals included acromotrichia and depigmentation, with varying degrees and distribution of skin lesions. Histological examination of the epidermis showed interrupted melanin production, mild dermal fibrosis, mild perivascular mononuclear inflammatory infiltrate, and pigmentary incontinence. None of the animals had the genotype for albinism. After 120 days of mineral supplementation based on the use of copper sulfate, the clinical signs of leucoderma regressed. There was no predisposition by breed, sex, or age for the occurrence of the disease. The regression of skin lesions after proper mineral supplementation suggests that copper deficiency may be considered an important factor for the occurrence of leucoderma in buffaloes in the Amazon biome.