Abstract A 4‐year‐old, male, entire guinea pig ( Cavia porcellus ) was presented in stuporous state with hypoglycaemia, hypothermia and hypotension. After stabilising the animal, a complete blood cell count, biochemistry, survey radiographs and an abdominal ultrasound were performed. The abdominal ultrasound revealed a 3.2 × 5.4 cm soft tissue mass occupying the caudal half from lateral to medial part of the right kidney. To investigate further, a computed tomography scan with intravenous contrast was performed and confirmed the invasion of the mass into the caudal vena cava. A right nephrectomy was performed and submitted for histopathology, and a diagnosis of renal liposarcoma was made. The animal, although stable during surgery, died after recovery from anaesthesia. Spontaneous renal liposarcoma is rarely reported in human and veterinary medicine. This case report describes the clinical signs, diagnostic evaluation, surgical procedure, and gross and histological features of renal liposarcoma in a guinea pig.