Reliable diagnostic biomarkers are essential for LCNEC, which typically shows high expression of multiple neuroendocrine markers, including neural cell adhesion molecule (NCAM/CD56), synaptophysin (Syn), chromogranin A (CgA), etc. Among them, CD56, expressed in 92−98% of LCNEC, may be the most sensitive marker for the diagnosis of LCNEC, but also expressed in nearly 10% of adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, leading to low specificity. Here, SYP is linked to large cell carcinoma.