This multicenter retrospective study investigated the association between immune‐checkpoint inhibitor monotherapy effectiveness and the expression status of thyroid transcription factor 1 (TTF‐1) in 108 patients with advanced lung adenocarcinoma and showed that programmed death‐ligand 1 tumor proportion score, objective response rate, progression‐free survival, and overall survival were significantly lower in patients with TTF‐1‐negative expression than those in TTF‐1‐positive patients. Here, TTF1 is linked to neoplasm.