PurposeScreening for paraneoplastic antibodies is often performed by means of indirect immunofluorescence on primate cerebellar slices. However, atypical immunofluorescence patterns, i.e. patterns that are not specifically related to paraneoplastic antibodies, are often reported. The clinical significance of these patterns is not clear. Therefore, the purpose of this study was to determine the significance and diagnostic value—in terms of a paraneoplastic neurological syndrome or other neurological disease being diagnosed in the patient—of such atypical immunofluorescence screening patterns on primate cerebellum.MethodsThis study is a retrospective single center study including atypical indirect immunofluorescence screening patterns of patients with a negative or absent typing assay for intraneuronal and anti-amphiphysin paraneoplastic antibodies. Patients with a positive typing assay or without final diagnosis were excluded. Included patients were grouped according to (i) reported immunofluorescence pattern and (ii) established diagnosis, after which contingency table analyses were performed to investigate an interrelation between reported pattern and diagnostic group.ResultsIn 3.7% of cases, patients with an atypical pattern obtained a final diagnosis of a paraneoplastic neurological syndrome. The presence of atypical patterns was more prominent in patients with epilepsy or peripheral neuropathies (pMonte Carlo simulation= 0.026), without, however, adding any diagnostic information.ConclusionsAn atypical indirect immunofluorescence pattern on primate cerebellum in the screening for paraneoplastic antibodies has only very minor relevance with respect to paraneoplastic neurological syndromes or any other neurological disease, recommending clinicians to interpret the results of positive screening assays for such antibodies with care.