In conclusion, IHC can be a reliable and effective method for ROS1 rearrangements preliminary screening in patients with NSCLC thanks to the high sensitivity and specificity of IHC using the D4D6 mAb, while cutoff should be set at diffusely (≥60 % tumor cells) 2–3+ cytoplasmic reactivity and an H-score ≥150. The gene discussed is ROS1; the disease is neoplasm.