A 42-year-old, male patient with no remarkable medical history noticed that a dark brown macule on his left anterior chest, which he had been there for 20 years, began fading after his second coronavirus disease 2019 (COVID-19) vaccination. One week after he received his third booster vaccination, his left axillary lymph node became swollen. Thinking that it was an adverse reaction to the vaccine, the patient did not seek any treatment. However, the swelling increased rapidly over a few months, prompting him to visit our hospital (). The patient had an indistinct, light-brown macule on the left anterior chest and a 13-cm left axillary mass with poor mobility. A biopsy specimen of the macule demonstrated an aggregation of melanophages only in the dermis and an absence of tumor cells. However, a biopsy of the axillary mass revealed metastatic melanoma. Based on these findings, an axillary lymph node metastasis of malignant melanoma originating in the left anterior chest lesion was diagnosed. Positron emission tomography (PET) demonstrated axillary lymph node accumulations (SUV max 13.2) with no metastasis to any other organ or accumulation in the primary tumor (the brown macule) (). Within one month after the initial visit, the axillary mass grew to 17 cm. Pleural effusion, ascites, and systemic edema were also present. The SpO2 had decreased to 88% on room air, and dyspnea, hypertension (blood pressure 158/111), tachycardia (heart rate 136 bpm), and congestive heart failure were also observed. Blood analysis demonstrated an elevated white blood cell count (11400/µL), hypoalbuminemia (Alb 2.2 g/dl), mildly elevated lactose dehydrogenase (LDH) (366 IU/L), elevated C-reactive protein (CRP) (5.64 mg/dl), and elevated N-terminal fragment-pro B-type natriuretic peptide (NT-proBNP) (766U/L). Cytology of the pleural fluid returned negative for tumor cells, and echocardiography demonstrated an ejection fraction of 52% and mildly reduced left ventricular contractility. An electrocardiogram (ECG) demonstrated a normal ST segment and sinus rhythm and no pulse irregularities or QT prolongation.?>The patient was admitted on an emergency basis for his life-threatening condition. Treatment with a combination of nivolumab (nivo) plus ipilimumab (ipi) was begun after the associated risk of cardiac dysfunction was explained to the patient prior to testing for BRAF mutations. Simultaneously, he received diuretics and antihypertensive drugs for his heart failure. The axillary tumor shrank to 11 cm after three courses of the therapy, resulting in a partial response (PR). Grade 3 anemia and grade 2 fever occurred as immune-related adverse events. However, no other, serious adverse events, including myocarditis, were observed, and the patient was able to continue treatment. Unfortunately, after four courses of the therapy, the axillary tumor began growing. In addition, the heart failure flared, and new, mediastinal lymph node metastases appeared. Progressive disease (PD) was diagnosed, and the treatment was switched to BRAFi/MEKi (encorafenib/vinimetinib) after the patient tested positive for BRAF V600E. The tumor shrank markedly, and the heart failure improved after one month of this treatment (, ). At month 4 after the start of the BRAFi/MEKi therapy, the patient achieved complete remission (CR), and at month 6, no PET accumulation was found at any site (). Although grade 3 hypertension was observed as a drug-related adverse event, it was controlled with antihypertensive medication. No other serious adverse events, including cardiovascular adverse events, were observed. The patient has continued to receive BRAFi/MEKi and has maintained CR for more than six months.