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An 8-year-old male neutered miniature Rex rabbit ( Oryctolagus cuniculus ) was evaluated for progressive left rear limb lameness. A smooth, hard mass was palpated over the proximolateral aspect of the left tibia. Initial radiographic evaluation of the area surrounding the mass revealed a proliferative bony lesion lateral to the tibia without evidence of pulmonary metastases. Cytology of the lesion was consistent with osseous proliferation. Follow up radiographs of the mass after the initial presentation, provided evidence of the mass increasing in size so a second cytologic evaluation was requested. The diagnostic interpretation of the second cytologic submission collected from the mass was osteosarcoma. A coxofemoral amputation was performed on the left rear limb of the rabbit, after which the patient recovered uneventfully from the procedure. Histopathologic evaluation of the mass confirmed osteoblastic osteosarcoma. There was no evidence of metastasis in radiographic images performed at 4 and slightly more than 6 months after the amputation procedure. The rabbit died 190 days after the amputation and several days after recovery from a gastrotomy for gastric bloat. A necropsy was not performed.