Hot topics of immunohistochemistry in lung cancer are discussed, including (i) the differential diagnosis between adenocarcinoma and squamous cell carcinoma (SqCC); (ii) neuroendocrine markers; (iii) driver genetic alterations (ALK, ROS1, and EGFR); (iv) PD-L1 (CD274) expression; (v) the differential diagnosis between lung carcinoma and malignant mesothelioma; and (vi) NUT carcinoma. This evidence concerns the gene CD274 and adenocarcinoma.