Paraneoplastic cerebellar degeneration (PCD) is a rare disease that is triggered by an abnormal immune response to a malignant tumor by cross-reaction of antibodies. The low prevalence of this condition has not allowed for large-scale randomized controlled trials. Suspecting a paraneoplastic syndrome followed by rapid diagnosis is crucial before the symptoms irreversibely progress. Indirect immunofluorescence (IIF) with HEp-2 ​cells is currently the most widely used screening technique for the detection of a wide range of nuclear and cytoplasmatic autoantibodies. Here, we present a case of a female Caucasian patient, 61 years of age, who started having sudden symptoms of PCD starting April 2016 that progressed through the course of 10 months before the final diagnosis. Assuming that antinuclear antibodies (ANA) testing could give rise to suspicion of an underlying malignancy but also to an underlying autoimmune etiology of PCD, we followed the ANA patterns of the patient during the course of disease and treatment protocols. A total of four ANA follow ups were done on serum dilution 1:100 and all showed weak positive results on hepatic cells and a mix of similar patterns that, through the course of time, differed slightly on HEp-2 ​cells. Finding positive antinuclear or anticytoplasmic auto-antibodies might guide toward an extensive and useless search for a systemic autoimmune disease ignoring the possibility of searching for paraneoplastic-specific antibodies. An unspecified mix of patterns should not be ignored and might, through further research, show to be more valuable in the ANA screening than is the case now. Weak positive results should not mislead into thinking that there is no overall effect on health, since quite the opposite was the case here. In our example, neither the tumor response to treatment, neurological presentation nor the immunological treatment had a strong effect on the ANA patterns which remained almost identical throughout the course of disease and treatment. Ultrastructural and molecular events in the pathogenesis of the disease could have caused certain minor changes in the pattern but are not of clinical value at the moment and further research is needed.