Pythiosis is a granulomatous lesion of the skin and subcutaneous tissues caused by Pythium insidiosum, a microorganism belonging to the Stramenopila Kingdom and the Oomycetes Class. The pathogen is commonly found in water environments, mainly in tropical areas of the world. Twenty eight cases of equine pythiosis were presented at the Large Animal Surgery Department of the School of Veterinary Medicine and Animal Science, São Paulo State University, Brazil in six years. Among the 28 animals, 13 presented distal lesions on the limbs, with four being immediately euthanized and seven dying due to loss of body condition leading to cachexia. The horses presented with one or more wounds in the body, distributed as follows: limbs (13 distal, four proximal), abdominal region (7), thoracic region (1), pectoral region (1), lumbar region (1), nasal region (1) and prepuce (1). The diagnosis was made by the association of the macroscopic aspects of the lesions with the histopathology, isolation of the pathogen and/or nested-PCR. Treatments included surgical removal of the lesion (16), potassium iodide 67 mg kg-1 PO sid (23), intravenous regional perfusion with 50 mg of amphotericin B (6) and immunotherapy (8). Pythiosis is a disease that develops quickly, but its diagnosis is time-consuming; therefore, establishing an early treatment with special attention to the involvement of distal regions of the limbs is important.