Iida Y, et al. - This study aimed to elucidate the characteristics of thyroid transcription factor 1 (TTF-1)-negative small cell lung cancer (SCLC). In a case control cohort matched for basic clinical factors, TTF-1-negative SCLC samples demonstrated significantly decreased expression of pro-gastrin-releasing peptide (ProGRP), synaptophysin, chromogranin A, and achaete-scute homolog like 1 (ASCL1). However, no significant correlation between Ki-67 labeling index and TTF-1 was identified. In a larger serial case cohort, TTF-1-negative SCLC cases were older at diagnosis. However, patients with TTF-1-negative and TTF-1-positive SCLC demonstrated no significant difference in the overall survival. Thereby suggesting decreased neuroendocrine differentiation in TTF-1-negative SCLC, but with no significant worse clinical outcomes.