To gain insight into the degree of clinical heterogeneity observed in therapeutic responses, we first analyzed radiographic responses of synchronous melanoma metastases to therapy in a large cohort of patients with metastatic melanoma (n = 60) that received first-line treatment with either targeted therapy with combined BRAF and MEK inhibitors or immune checkpoint blockade with anti-programmed cell death (PD)-1-based therapy (n = 30 per group). The gene discussed is MAP2K7; the disease is metastatic melanoma.