Protothecosis is an infectious disease caused by microalgae of the genus Prototheca. Prototheca can be found in soil and water and transiently colonize animals. Cutaneous protothecosis can involve not only the skin but also the underlying subcutaneous tissue and lymph nodes. This can lead to clinical signs and a microscopic tissue image that closely resembles a fungal infection. Treatment typically involves antifungal medications. We report the first case of fatal disseminated protothecosis caused by Prototheca wickerhamii in the city of Rosario, Argentina in a 5-year-old female poodle dog. The dog exhibited ocular signs of uveitis and lymphadenitis. To reach a clinical and etiological diagnosis, imaging studies, routine laboratory tests and serological tests were performed. A mycological analysis was conducted on the material obtained by puncturing three lymph nodes. Additionally, morphological, metabolic, and molecular analyses were performed. Antifungal susceptibility testing was also conducted using broth microdilution and diffusion methods. Phenotypic, metabolic, and sequencing techniques identified the isolated organism as P. wickerhamii. This isolate displayed susceptibility to amphotericin, variable susceptibility to itraconazole and voriconazole, and resistance to fluconazole and caspofungin. The frequent presence of pets in our homes highlights the need for a more comprehensive diagnostic approach. This is important because, from a public health perspective, dogs could serve as indicators of algal presence in the environments they frequently share with humans.