The patient presented at age 43 with a new left varicocele having already suffered one episode of gross hematuria. An abdominal ultrasonography revealed the presence of a left renal mass and a 2-cm renal mass in his right kidney. CT scan demonstrated two small 4-mm lung lesions. This was followed by a left radical nephrectomy. Pathological examination of the mass demonstrated a clear-cell RCC. A 1-cm isolated metastatic nodule was also found in the adrenal gland. Two years later, the lung lesions had increased to 5 mm, a further three 2-mm nodular lesions had appeared in the lungs and no growth in the small right renal lesion was found. Following this, MR imaging demonstrated an intradural intramedullary lesion (later confirmed to be consistent with a hemangioblastoma from the inferior portion of the T-5 to T-6) with a prominent feeding vessel. The patient underwent a T5–8 laminectomy. Clinical diagnosis of VHL was reached at this point. Genetic analysis found a deleting mutation in the first exon (nt. 394-406) of the VHL locus, truncating 16 amino acids (N61-77) from the first beta sheet in the VHL protein. This mutation was translated to the updated reference sequence (NM_000551.3) as p.P61_C77del (c.181_231del). This mutation was not present in any of the family members tested including the patient’s two children. At this point, MRI showed no masses, ophthalmological examination showed normal results and a congenital malformation with C-1 occipitalization and C2–3 fusion were identified. The patient underwent resection of the right renal mass, which was consistent with a clear-cell carcinoma. One year later, two cerebral lesions were diagnosed and were consistent with RCC metastases in the right occipital lobe for which he received radiation therapy. No new lesions had appeared in the spinal cord and his chest disease was found to be stable. ACMG evidence codes: 'PM6' since this mutation was declared to be non-familial but kindred testing was not specified (assumed de novo), 'PP4' since the patients phenotypes are highly specific for a disease with a single genetic etiology.