Autoimmune toxicities, while common following treatment with cancer immunotherapies, are not well-characterized in patients treated with BRAF/MEK inhibitors. Emerging data suggest that autoimmune effects may be linked with superior responses to both treatment modalities; however, there is little evidence describing mechanisms of immune-related toxicity for patients on BRAF/MEK inhibitors. Here we describe the experience of a 59-year-old HLA-A2, A29, B27-positive male patient with recurrent/metastatic melanoma. After progression on checkpoint inhibitor therapy, he was treated with dabrafenib/trametinib followed by encorafenib/binimetinib, which were well-tolerated. 18 months into BRAF/MEK inhibitor therapy, he developed a series of sudden-onset, severe toxicities including bilateral panuveitis, cytopenias, joint pain, skin rash, hypercalcemia and interstitial nephritis, which led to BRAF/MEKi cessation. At that time, the patient was found to have a complete response, which is ongoing at