From a predictive standpoint, some reports have linked high tumour mutational burden with response to immune checkpoint blockade, and although a general correlation between tumour PD-L1 expression and outcome has been reported, PD-L1 expression has relatively little predictive value in identifying potential responders. Subsequently, microsatellite instability has been proposed to be classified as a European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (known as ESCAT) tier IC target is this in squamous cell carcinoma of the head and neck. Because complete response is a rare event (1–5%) in immune checkpoint blockade-treated squamous cell carcinoma of the head and neck, microsatellite instability could be speculated to have a role in the exceptional response observed in the case presented here, especially when comparing the exceptional result observed in case 1 with the relatively poor efficacy observed in case 2, in which the patient had microsatellite stability. In addition to identifying microsatellite instability and tumour mutational burden, comprehensive NGS profiling might also yield useful information about clinically informative or potentially actionable genetic alterations, such as ARID1A, PTEN, and FGFR1 in this case (figure). ...longitudinal assessment of the genomic landscape identifying loss of CBL, acquisition of ASXL1, FGFR1, and SMARCB1 alterations, and increasing allelic frequency of the MSH6 mutation might also provide evolutionary clues to tumour aggressiveness and heterogeneity (appendix p 1).