A man in his 80s presented with 2 years of recurrent cutaneous squamous cell carcinoma...a somatic missense (R135C) mutation in the ERBB3/HER3 gene, as well as multiple other mutations (Table 1) and a high tumor mutation burden. In an effort to target the ERBB3/HER3 mutation, therapy with 1,250 mg of lapatinib daily in combination with 240 mg nivolumab every 2 weeks was initiated. Significant improvement in the clinical size of the lesion was noted after 2 months of lapatinib therapy. After 6 months, there was continued clinical improvement (Fig. 2) and MRI showed significant regression of muscle, nerve, and bone involvement (Fig. 3).