This episode combines two articles and discusses the importance of laboratory expertise in accurately diagnosing autoimmune neurological syndromes, particularly autoimmune encephalitis and paraneoplastic syndromes, which are often difficult to identify due to overlapping symptoms and low prevalence. The author reviews two companion studies evaluating commercially available tissue-based assays for detecting antibodies against intracellular and surface antigens. The studies reveal significant limitations in the sensitivity and specificity of these commercial tests when used as standalone screening tools, highlighting the risk of both false positives and false negatives. Ultimately, the piece emphasizes the need for multimodal testing, skilled interpretation of results, and interdisciplinary communication between clinicians and laboratory staff to ensure reliable diagnosis and improve patient outcomes.