In November 2008, an otherwise healthy 60-year old Caucasian female presented at the department of otorhinolaryngology due to right-sided limited nasal breathing accompanied by bloody nasal discharge. Aside from tonsillectomy and partial dentures, her past medical history, including alcohol and nicotine, was unremarkable. Examination with nasal specula showed a tumor covered with bloody secretions, completely occupying the right nasal meatus in the absence of cervical lymphadenopathy assessed by palpation. Magnetic resonance imaging (MRI) revealed nasal septal deviation due to a 5 × 2.2 × 4.5 cm measuring mass located in the right nasal meatus and right ethmoid sinus, highly suspicious of malignant origin. The tumor was removed by functional endoscopic sinus surgery. Based on histological and immunohistochemical results, showing epithelial as well as mesenchymal differentiation, and absence of molecular translocation t(X,18), the diagnosis of a spindle cell carcinoma, formerly called carcinosarcoma, was made (cT3 N0 M0). Following this diagnosis, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging showed a solitary 1 × 1.3 cm residual lesion in the right nasal meatus which necessitated surgical re-resection followed by adjuvant radiotherapy without adjuvant chemotherapy, leading to a cumulative radiation dose of 61.1 gray (Gy) in the tumor bed. At follow-up in December 2009, a solitary firm and immobile mass beneath the left jaw angle was palpated on physical examination. Two spherical 1.5 cm measuring lymph nodes were detected by MRI and intense tracer uptake was demonstrated by 18F-FDG PET/CT imaging. Prior to the planned neck dissection, in January 2010, the previously asymptomatic patient complained about progressive gait instability accompanied by vertigo and nausea. Detailed neurologic examination revealed central nystagmus, bilateral dysdiadochokinesia, distal pallhypesthesia affecting the lower extremities, bilateral dysmetria on finger-nose-test, an ataxic gait and a positive Romberg test. Although ischemia, hemorrhage, malignancy as well as other morphological abnormalities of the cerebellum and cerebrum were immediately ruled out by CT and MRI of the head, the patient’s neurological symptoms deteriorated, necessitating the use of a walking aid. In February, left-sided level II neck dissection took place and histologic work-up of the suspicious lymph nodes confirmed locoregional recurrence of the previously described spindle cell carcinoma. A short-term neurologic reevaluation confirmed persistence of cerebellar symptoms. In order to rule out infectious causes and autoimmune processes, serologic testing for syphilis and Lyme disease were done, but results were unremarkable. In addition, two sequential lumbar punctures were performed, cerebrospinal fluid analysis revealed cell counts (erythrocytes: 3/μl and 12/μl; monocytes: few; lymphocytes: few) and serum chemistry (total protein: 48 mg/dl and 44 mg/dl; glucose: 56 mg/dl and 57 mg/dl; lactate: 1.7 mmol/l and 1.8 mmol/l) within normal limits in the absence of malignant cells. Polymerase chain reaction and serology testing for commonly tested viruses (Herpes simplex virus, Varicella zoster virus, Ebstein-Barr virus, Cytomegaly virus, Tick-borne encephalitis virus, Enterovirus), protozoa (Toxoplasma gondii) and bacteria (Listeria, Borrelia) was negative. Magnetic resonance imaging of the spine was performed but did not show any morphological abnormalities either. Subsequently, the patient’s serum was analyzed for onconeural antibodies in order to investigate the possible role of a paraneoplastic syndrome in this case. The presence of anti-Hu antibodies was demonstrated by a tissue based assay for intracellular antigens, using an avidin-biotin peroxidase technique on frozen sections of rat cerebellum (antibody titer 1:2000; Fig. /) and confirmed by a recombinant immunoblot (ravo Diagnostika GmbH, Freiburg, Germany). Nerve conduction testing revealed the presence of demyelinating as well as axonal polyneuropathy of the lower extremities, affecting motor and sensory nerves. With regard to all findings, the patient’s neurological presentation was classified as paraneoplastic cerebellar degeneration. In the absence of other potential causative neurotoxic factors in the patient’s history, the polyneuropathy documented in parallel was also considered of paraneoplastic origin in association with detectable anti-Hu antibodies in the patient’s serum. Adjuvant concomitant chemoradiotherapy of the left neck with 64.6 Gy was initiated and the patient received two cycles of platinum-based chemotherapy at 21-day intervals starting in March 2010. In the light of the patient’s documented neuropathy, carboplatin AUC (area under the curve) 5 was preferred over cisplatin for concomitant use with radiotherapy due to its lower potential for peripheral neurotoxicity. Complete remission was confirmed after multimodal cancer treatment and structural cerebellar and cerebral abnormalities were again ruled out by MRI of the head. After several months, the patient’s neurological symptoms, especially ataxia, had reached a plateau and she maintained her ambulatory ability by the use of a wheeled walker. On a regular basis, close interdisciplinary follow-up visits at the oncology and otorhinolaryngology department took place. Our patient remained in complete remission for the following 3 years without deterioration of ataxic gait or vertigo. Follow-up study of serum only revealed a slight decline of anti-Hu antibody titer (1:500). Immunohistochemical analysis on formalin-fixed and paraffin-embedded biopsy material of the primary tumor and the lymph node metastasis (not shown) with biotinylated anti-Hu IgG (obtained from an anti-Hu positive serum) showed strong nuclear expression of the Hu-antigen in the majority of tumor cells. However, in comparison to the primary tumor, the lymph node metastasis contained a substantial fraction dedifferentiated cells characterized by enlarged nuclei and enlarged cytoplasm. As the patient’s neurological complaints remained stable for more than 3 years after effective anticancer therapy and considering the unsatisfying treatment responses described in the literature, we decided against immunosuppressive therapy or plasmapheresis.